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1
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Abdelqader EM, Mahmoud WS, Gebreel HM, Kamel MM, Abu-Elghait M. Correlation between gut microbiota dysbiosis, metabolic syndrome and breast cancer. Sci Rep 2025; 15:6652. [PMID: 39994329 PMCID: PMC11850770 DOI: 10.1038/s41598-025-89801-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2024] [Accepted: 02/07/2025] [Indexed: 02/26/2025] Open
Abstract
Breast cancer is a widespread cancer with a high death rate globally. The incidence of breast cancer is expected to increase, particularly in low and middle-income countries due to environmental factors and lifestyle changes. Several risk factors, such as age, family history, hormonal and reproductive factors, have been identified to influence breast cancer development. Metabolic syndrome, is a metabolic disorder that has also been linked to breast cancer risk. The gut microbiome has been suggested as one of the environmental factors leading to breast cancer. The human microbiome is mainly colonized in the intestine by various bacterial species, including Lactobacillus, Bifidobacterium, and Streptococcus and protect the host against pathogenic microorganisms and regulate the immune system. This study included 50 female breast cancer patients and 50 healthy controls with matched ages. Stool fresh samples were taken from test and control groups and stored at - 20 °C until further investigations. DNA of the bacteria in stool samples was extracted using reverse transcription-quantitative polymerase chain reaction to check for the bacterial 16s rRNA gene. The exclusion criteria included other malignancies, recent intestinal surgery, infectious diarrhea, prolonged use of antibiotics, substance addiction, and pregnancy or lactation. Our findings exhibited that breast cancer patients had a higher incidence of metabolic syndrome (60%) compared to cancer-free controls (40%). Furthermore, breast cancer patients had significantly lower Bifidobacterium and Lactobacillus counts than the controls. No significant difference was found in Streptococcus counts between groups. These findings support the relationship between breast cancer and metabolic syndrome and suggest the potential involvement of Lactobacillus and Bifidobacterium in breast cancer pathophysiology. Our study supports the relation between breast cancer and disorder of metabolic syndrome and suggests the potential involvement of Lactobacillus and Bifidobacterium in breast cancer pathophysiology. Further research is necessary to investigate the complex interactions between genes, the environment, and the gut microbiome in breast cancer development. Understanding these interactions could lead to the progress of novel strategies for breast cancer prevention and treatment.
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Affiliation(s)
- Eslam M Abdelqader
- Department of Microbiology, Faculty of Science, Ain Shams University, Cairo, Egypt.
| | - Walaa S Mahmoud
- Biological Anthropology Department National Research Centre, Dokki, Giza, Egypt
| | - Hassan M Gebreel
- Department of Microbiology, Faculty of Science, Ain Shams University, Cairo, Egypt
| | - Mahmoud M Kamel
- Clinical Pathology Development, National Cancer Institute Cairo University, Cairo, Egypt
- Laboratory Development Bahyea Centre for Early Detection and Cancer Treatment, Cairo, Egypt
| | - Mohammed Abu-Elghait
- Department of Botany and Microbiology, Faculty of Science, Al-Azhar University, Cairo, 11884, Egypt
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2
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Fukao M, Tagawa K, Sunada Y, Uehara K, Sugimoto T, Zendo T, Nakayama J, Segawa S. Genomic Insights into Probiotic Lactococcus lactis T-21, a Wild Plant-Associated Lactic Acid Bacterium, and Its Preliminary Clinical Safety for Human Application. Microorganisms 2025; 13:388. [PMID: 40005754 PMCID: PMC11858486 DOI: 10.3390/microorganisms13020388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2025] [Revised: 01/30/2025] [Accepted: 02/05/2025] [Indexed: 02/27/2025] Open
Abstract
Lactococcus lactis T-21 is a lactic acid bacterium isolated from wild cranberries in Japan that demonstrates significant immunomodulatory properties and has been incorporated into commercial health products. However, probiogenomic analyses specific to T-21 have remained largely unexplored. This study performed a thorough genomic characterisation of T-21 and evaluated its safety in initial clinical trials. Genomic analysis revealed substantial genetic diversity and metabolic capabilities, including enhanced fermentative potential demonstrated by its ability to metabolise a wide range of plant-derived carbohydrates, and genetic determinants associated with exopolysaccharide biosynthesis and nisin production, distinguishing T-21 from domesticated dairy strains. These attributes, reflective of its wild plant origin, may contribute to its metabolic versatility and unique probiotic functionalities. A preliminary clinical trial assessing the safety of T-21-fermented milk in healthy Japanese adults indicated no significant adverse outcomes, corroborating its safety for human consumption. Together, these findings support the feasibility of utilising non-dairy, wild plant-origin strains in dairy fermentation processes as probiotics. This study expands our understanding of the genomic basis for T-21's probiotic potential and lays the groundwork for further investigations into its functional mechanisms and potential applications in promoting human health.
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Affiliation(s)
- Masanori Fukao
- Nissin York Co., Ltd., 3-6-11 Higashi-Nihonbashi Chuo-ku, Tokyo 103-0004, Japan; (K.T.); (S.S.)
| | - Keisuke Tagawa
- Nissin York Co., Ltd., 3-6-11 Higashi-Nihonbashi Chuo-ku, Tokyo 103-0004, Japan; (K.T.); (S.S.)
| | - Yosuke Sunada
- Global Innovation Center, Nissin Foods Holdings Co., Ltd., 2100 Tobukimachi, Hachioji-shi 192-0001, Tokyo, Japan; (Y.S.); (K.U.); (T.S.)
| | - Kazuya Uehara
- Global Innovation Center, Nissin Foods Holdings Co., Ltd., 2100 Tobukimachi, Hachioji-shi 192-0001, Tokyo, Japan; (Y.S.); (K.U.); (T.S.)
| | - Takuya Sugimoto
- Global Innovation Center, Nissin Foods Holdings Co., Ltd., 2100 Tobukimachi, Hachioji-shi 192-0001, Tokyo, Japan; (Y.S.); (K.U.); (T.S.)
| | - Takeshi Zendo
- Laboratory of Microbial Technology, Division of Systems Bioengineering, Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan; (T.Z.); (J.N.)
| | - Jiro Nakayama
- Laboratory of Microbial Technology, Division of Systems Bioengineering, Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan; (T.Z.); (J.N.)
| | - Shuichi Segawa
- Nissin York Co., Ltd., 3-6-11 Higashi-Nihonbashi Chuo-ku, Tokyo 103-0004, Japan; (K.T.); (S.S.)
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3
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Schwartz L, Norman JO, Hasan S, Adamek OE, Dzuong E, Lowenstein JC, Yost OG, Sankaran B, McLaughlin KJ. Carbohydrate Deacetylase Unique to Gut Microbe Bacteroides Reveals Atypical Structure. Biochemistry 2025; 64:180-191. [PMID: 39663570 PMCID: PMC11713874 DOI: 10.1021/acs.biochem.4c00519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Revised: 11/27/2024] [Accepted: 12/03/2024] [Indexed: 12/13/2024]
Abstract
Bacteroides are often the most abundant, commensal species in the gut microbiome of industrialized human populations. One of the most commonly detected species is Bacteroides ovatus. It has been linked to benefits like the suppression of intestinal inflammation but is also correlated with some autoimmune disorders, for example irritable bowel disorder (IBD). Bacterial cell surface carbohydrates, like capsular polysaccharides (CPS), may play a role in modulating these varied host interactions. Recent studies have begun to explore the diversity of CPS loci in Bacteroides; however, there is still much unknown. Here, we present structural and functional characterization of a putative polysaccharide deacetylase from Bacteroides ovatus (BoPDA) encoded in a CPS biosynthetic locus. We solved four high resolution crystal structures (1.36-1.56 Å) of the enzyme bound to divalent cations Co2+, Ni2+, Cu2+, or Zn2+ and performed carbohydrate binding and deacetylase activity assays. Structural analysis of BoPDA revealed an atypical domain architecture that is unique to this enzyme, with a carbohydrate esterase 4 (CE4) superfamily catalytic domain inserted into a carbohydrate binding module (CBM). Additionally, BoPDA lacks the canonical CE4 His-His-Asp metal binding motif and our structures show it utilizes a noncanonical His-Asp dyad to bind metal ions. BoPDA is the first protein involved in CPS biosynthesis from B. ovatus to be characterized, furthering our understanding of significant biosynthetic processes in this medically relevant gut microbe.
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Affiliation(s)
- Lilith
A. Schwartz
- Department
of Chemistry, Vassar College, 124 Raymond Ave, Poughkeepsie, New York 12604, United States
| | - Jordan O. Norman
- Biochemistry
Program, Vassar College, 124 Raymond Ave, Poughkeepsie, New York 12604, United States
| | - Sharika Hasan
- Biochemistry
Program, Vassar College, 124 Raymond Ave, Poughkeepsie, New York 12604, United States
| | - Olive E. Adamek
- Biochemistry
Program, Vassar College, 124 Raymond Ave, Poughkeepsie, New York 12604, United States
| | - Elisa Dzuong
- Department
of Chemistry, Vassar College, 124 Raymond Ave, Poughkeepsie, New York 12604, United States
| | - Jasmine C. Lowenstein
- Department
of Chemistry, Vassar College, 124 Raymond Ave, Poughkeepsie, New York 12604, United States
| | - Olivia G. Yost
- Biochemistry
Program, Vassar College, 124 Raymond Ave, Poughkeepsie, New York 12604, United States
| | - Banumathi Sankaran
- Molecular
Biophysics and Integrated Bioimaging, Berkeley Center for Structural
Biology, Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States
| | - Krystle J. McLaughlin
- Department
of Chemistry, Vassar College, 124 Raymond Ave, Poughkeepsie, New York 12604, United States
- Biochemistry
Program, Vassar College, 124 Raymond Ave, Poughkeepsie, New York 12604, United States
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4
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Cheng C, Du J, Tao J, Cheng D. Growth Characteristics of Sheep-Derived Bacteroides fragilis and Preliminary Research on Effects in Mice and Lambs. Microorganisms 2025; 13:87. [PMID: 39858855 PMCID: PMC11767915 DOI: 10.3390/microorganisms13010087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2024] [Revised: 01/03/2025] [Accepted: 01/03/2025] [Indexed: 01/27/2025] Open
Abstract
With the growing demand for sheep, the sheep farming industry has developed rapidly. However, lamb diarrhea, a disease with high mortality rates, significantly hampers the industry's growth. Traditional antibiotic treatments often disrupt the Intestinal microbiota, induce antibiotic resistance, and cause adverse side effects, highlighting the urgent need to develop alternative therapies. Bacteroides fragilis, a candidate next-generation probiotic, has been closely associated with intestinal health. This study investigated the growth characteristics and probiotic effects of a sheep-derived Bacteroides fragilis isolate, focusing on its efficacy in alleviating lamb diarrhea and infectious intestinal diseases. The experiments demonstrated that the Bacteroides fragilis isolate grows well under mildly acidic conditions (pH 6-8), exhibits some tolerance to bile salts, and has survival rates of 38.89% and 92.22% in simulated gastric and intestinal fluids, respectively, indicating its potential as a probiotic. In a mouse model, Bacteroides fragilis intervention significantly alleviated colonic inflammation caused by Enterohemorrhagic Escherichia coli infection, enhanced tight junction protein expression, mitigated oxidative stress, and improved intestinal barrier function, with high-dose interventions showing superior effects. In lamb trials, Bacteroides fragilis intervention stopped diarrhea in four out of five lambs, partially restored intestinal microbiota diversity, and reduced the abundance of potential pathogens such as Aerococcus suis and Corynebacterium camporealensis. Therefore, Bacteroides fragilis exhibited remarkable effects in regulating intestinal homeostasis, alleviating inflammation, and promoting recovery from diarrhea.
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Affiliation(s)
- Cheng Cheng
- College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China
- Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China
| | - Jinye Du
- College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China
| | - Jianping Tao
- College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China
- Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China
| | - Darong Cheng
- College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China
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5
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Shen D, Seco BMS, Teixeira Alves LG, Yao L, Bräutigam M, Opitz B, Witzenrath M, Fries BC, Seeberger PH. Semisynthetic Glycoconjugate Vaccine Lead against Klebsiella pneumoniae Serotype O2afg Induces Functional Antibodies and Reduces the Burden of Acute Pneumonia. J Am Chem Soc 2024; 146:35356-35366. [PMID: 39666976 DOI: 10.1021/jacs.4c13972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2024]
Abstract
Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) bacteria are a serious global health concern due to their drug-resistance to nearly all available antibiotics, fast spread, and high mortality rate. O2afg is a major CR-Kp serotype in the sequence type 258 group (KPST258) that is weakly immunogenic in humans. Here, we describe the creation and evaluation of semisynthetic O2afg glycoconjugate vaccine leads containing one and two repeating units of the polysaccharide epitope that covers the surface of the bacteria conjugated to the carrier protein CRM197. The semisynthetic glycoconjugate containing two repeating units induced functional IgG antibodies in rabbits with opsonophagocytic killing activity and enhanced complement activation and complement-mediated killing of CR-Kp. Passive immunization reduced the burden of acute pneumonia in mice and may represent an alternative to antimicrobial therapy. The semisynthetic glycoconjugate vaccine lead against CR-Kp expressing O2afg antigen is awaiting preclinical development.
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Affiliation(s)
- Dacheng Shen
- Department of Bimolecular System, Max Planck Institute of Colloids and Interfaces; 14476 Potsdam, Germany
- Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany
| | - Bruna M S Seco
- Department of Bimolecular System, Max Planck Institute of Colloids and Interfaces; 14476 Potsdam, Germany
- Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany
| | - Luiz Gustavo Teixeira Alves
- Department of Infectious Diseases, Respiratory Medicine and Critical Care, Charite-Universitätsmedizin Berlin; 10117 Berlin, Germany
| | - Ling Yao
- Department of Bimolecular System, Max Planck Institute of Colloids and Interfaces; 14476 Potsdam, Germany
- Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany
| | - Maria Bräutigam
- Department of Bimolecular System, Max Planck Institute of Colloids and Interfaces; 14476 Potsdam, Germany
- Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany
| | - Bastian Opitz
- Department of Infectious Diseases, Respiratory Medicine and Critical Care, Charite-Universitätsmedizin Berlin; 10117 Berlin, Germany
- German Center for Lung Research (DZL), 12203 Berlin, Germany
| | - Martin Witzenrath
- Department of Infectious Diseases, Respiratory Medicine and Critical Care, Charite-Universitätsmedizin Berlin; 10117 Berlin, Germany
- German Center for Lung Research (DZL), 12203 Berlin, Germany
| | - Bettina C Fries
- Department of Medicine, Infectious Disease Division, Stony Brook University; Stony Brook, New York 11794, United States
- Veteran's Administration Medical Center, Northport, New York 11768, United States
| | - Peter H Seeberger
- Department of Bimolecular System, Max Planck Institute of Colloids and Interfaces; 14476 Potsdam, Germany
- Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany
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6
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Benga L, Rehm A, Gougoula C, Westhoff P, Wachtmeister T, Benten WPM, Engelhardt E, Weber APM, Köhrer K, Sager M, Janssen S. The host genotype actively shapes its microbiome across generations in laboratory mice. MICROBIOME 2024; 12:256. [PMID: 39639355 PMCID: PMC11619136 DOI: 10.1186/s40168-024-01954-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Accepted: 10/18/2024] [Indexed: 12/07/2024]
Abstract
BACKGROUND The microbiome greatly affects health and wellbeing. Evolutionarily, it is doubtful that a host would rely on chance alone to pass on microbial colonization to its offspring. However, the literature currently offers only limited evidence regarding two alternative hypotheses: active microbial shaping by host genetic factors or transmission of a microbial maternal legacy. RESULTS To further dissect the influence of host genetics and maternal inheritance, we collected two-cell stage embryos from two representative wild types, C57BL6/J and BALB/c, and transferred a mixture of both genotype embryos into hybrid recipient mice to be inoculated by an identical microbiome at birth. CONCLUSIONS Observing the offspring for six generations unequivocally emphasizes the impact of host genetic factors over maternal legacy in constant environments, akin to murine laboratory experiments. Interestingly, maternal legacy solely controlled the microbiome in the first offspring generation. However, current evidence supporting maternal legacy has not extended beyond this initial generation, resolving the aforementioned debate. Video Abstract.
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Affiliation(s)
- Laurentiu Benga
- Central Unit for Animal Research and Animal Welfare Affairs, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
| | - Anna Rehm
- Algorithmic Bioinformatics, Justus Liebig University Giessen, Giessen, Germany
| | - Christina Gougoula
- Central Unit for Animal Research and Animal Welfare Affairs, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Philipp Westhoff
- Cluster of Excellence on Plant Science, Institute of Plant Biochemistry, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Thorsten Wachtmeister
- Genomics and Transcriptomics Laboratory, Biological and Medical Research Center, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - W Peter M Benten
- Central Unit for Animal Research and Animal Welfare Affairs, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Eva Engelhardt
- Central Unit for Animal Research and Animal Welfare Affairs, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Andreas P M Weber
- Cluster of Excellence on Plant Science, Institute of Plant Biochemistry, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Karl Köhrer
- Genomics and Transcriptomics Laboratory, Biological and Medical Research Center, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Martin Sager
- Central Unit for Animal Research and Animal Welfare Affairs, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Stefan Janssen
- Algorithmic Bioinformatics, Justus Liebig University Giessen, Giessen, Germany.
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7
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Wang Y, Liu R, Xie Z, Du L, Wang Y, Han J, Zhang L. Structure characterization and immunological activity of capsular polysaccharide from live and heat-killed Lacticaseibacillus paracasei 6235. Int J Biol Macromol 2024; 277:134010. [PMID: 39032891 DOI: 10.1016/j.ijbiomac.2024.134010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Revised: 06/22/2024] [Accepted: 07/17/2024] [Indexed: 07/23/2024]
Abstract
Capsular polysaccharide (CPS) as a probiotic component has the ability to regulate the function of the host's immune system. However, how the structure and function of heat-killed CPS are altered remains unclear. In the present study, CPS were isolated and purified from live (LCPS) and heat-killed (HCPS) Lacticaseibacillus paracasei 6235. The differences in structure and immunomodulation between LCPS and HCPS were compared and analyzed. The results demonstrate that after heat killed, the molecular weight of CPS decreased from 23.4 kDa to 17.5 kDa, with the disappearance of galactosamine in the monosaccharide composition, and changes in the microstructure. Methylation analysis and nuclear magnetic resonance analysis revealed that the LCPS and HCPS are similar in structure, which main units of →3,4)-α-D-Glcp-(1→4)-α-D-Galp-(1→3)-β-L-Rhap-(1→6)-β-D-Galp-(1→, and repeating units of →3,4)-α-D-Glcp-(1→, →3)-β-L-Rhap-(1→, and →4)-α-D-Galp-(1→ residues. Furthermore, both LCPS and HCPS significantly downregulated the expression of pro-inflammatory cytokines in RAW264.7 cells induced by LPS. Specifically, HCPS reduced the levels of IL-6 and IL-1β by 79.38 % and 88.42 %, respectively, compared to LCPS. Concurrently, both LCPS and HCPS effectively mitigated inflammatory responses through the NF-κB and MAPK signaling pathways. Moreover, compared to LCPS, HCPS increased the protein expression levels of NF-κB/p-NF-κB and IκB/p-IκB by 26.14 % and 28.92 %, respectively. These results suggest that CPS has a role in modulating immune responses and that HCPS is more effective. This study can be further developed into new products related to postbiotics.
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Affiliation(s)
- Yucong Wang
- College of Food Science, Northeast Agricultural University, Harbin 150030, China
| | - Rongxu Liu
- Heilongjiang Green Food Science Research Institute, Harbin 150030, China
| | - Zhixin Xie
- College of Food Science, Northeast Agricultural University, Harbin 150030, China
| | - Lei Du
- College of Food Science, Northeast Agricultural University, Harbin 150030, China
| | - Yingnan Wang
- Heilongjiang Green Food Science Research Institute, Harbin 150030, China
| | - Jianchun Han
- College of Food Science, Northeast Agricultural University, Harbin 150030, China; Heilongjiang Green Food Science Research Institute, Harbin 150030, China.
| | - Lili Zhang
- College of Food Science, Northeast Agricultural University, Harbin 150030, China.
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8
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Chen Y, Xiao L, Zhou M, Zhang H. The microbiota: a crucial mediator in gut homeostasis and colonization resistance. Front Microbiol 2024; 15:1417864. [PMID: 39165572 PMCID: PMC11333231 DOI: 10.3389/fmicb.2024.1417864] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Accepted: 07/23/2024] [Indexed: 08/22/2024] Open
Abstract
The gut microbiota is a complex and diverse community of microorganisms that colonizes the human gastrointestinal tract and influences various aspects of human health. These microbes are closely related to enteric infections. As a foreign entity for the host, commensal microbiota is restricted and regulated by the barrier and immune system in the gut and contributes to gut homeostasis. Commensals also effectively resist the colonization of pathogens and the overgrowth of indigenous pathobionts by utilizing a variety of mechanisms, while pathogens have developed strategies to subvert colonization resistance. Dysbiosis of the microbial community can lead to enteric infections. The microbiota acts as a pivotal mediator in establishing a harmonious mutualistic symbiosis with the host and shielding the host against pathogens. This review aims to provide a comprehensive overview of the mechanisms underlying host-microbiome and microbiome-pathogen interactions, highlighting the multi-faceted roles of the gut microbiota in preventing enteric infections. We also discuss the applications of manipulating the microbiota to treat infectious diseases in the gut.
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Affiliation(s)
- Yiding Chen
- Department of Gastroenterology, West China Tianfu Hospital, Sichuan University, Chengdu, China
| | - Ling Xiao
- Department of Gastroenterology, West China Tianfu Hospital, Sichuan University, Chengdu, China
| | - Min Zhou
- Department of Gastroenterology, West China Tianfu Hospital, Sichuan University, Chengdu, China
| | - Hu Zhang
- Department of Gastroenterology, West China Tianfu Hospital, Sichuan University, Chengdu, China
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
- Center for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu, China
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9
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Wasén C, Beauchamp LC, Vincentini J, Li S, LeServe DS, Gauthier C, Lopes JR, Moreira TG, Ekwudo MN, Yin Z, da Silva P, Krishnan RK, Butovsky O, Cox LM, Weiner HL. Bacteroidota inhibit microglia clearance of amyloid-beta and promote plaque deposition in Alzheimer's disease mouse models. Nat Commun 2024; 15:3872. [PMID: 38719797 PMCID: PMC11078963 DOI: 10.1038/s41467-024-47683-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Accepted: 04/03/2024] [Indexed: 05/12/2024] Open
Abstract
The gut microbiota and microglia play critical roles in Alzheimer's disease (AD), and elevated Bacteroides is correlated with cerebrospinal fluid amyloid-β (Aβ) and tau levels in AD. We hypothesize that Bacteroides contributes to AD by modulating microglia. Here we show that administering Bacteroides fragilis to APP/PS1-21 mice increases Aβ plaques in females, modulates cortical amyloid processing gene expression, and down regulates phagocytosis and protein degradation microglial gene expression. We further show that administering Bacteroides fragilis to aged wild-type male and female mice suppresses microglial uptake of Aβ1-42 injected into the hippocampus. Depleting murine Bacteroidota with metronidazole decreases amyloid load in aged 5xFAD mice, and activates microglial pathways related to phagocytosis, cytokine signaling, and lysosomal degradation. Taken together, our study demonstrates that members of the Bacteroidota phylum contribute to AD pathogenesis by suppressing microglia phagocytic function, which leads to impaired Aβ clearance and accumulation of amyloid plaques.
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Affiliation(s)
- Caroline Wasén
- Ann Romney Center for Neurologic Diseases, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA
- Department of Life Sciences, Chalmers University of Technology, Gothenburg, Sweden
- Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Leah C Beauchamp
- Ann Romney Center for Neurologic Diseases, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Julia Vincentini
- Ann Romney Center for Neurologic Diseases, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Shuqi Li
- Ann Romney Center for Neurologic Diseases, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Danielle S LeServe
- Ann Romney Center for Neurologic Diseases, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Christian Gauthier
- Ann Romney Center for Neurologic Diseases, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Juliana R Lopes
- Ann Romney Center for Neurologic Diseases, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Thais G Moreira
- Ann Romney Center for Neurologic Diseases, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Millicent N Ekwudo
- Ann Romney Center for Neurologic Diseases, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Zhuoran Yin
- Ann Romney Center for Neurologic Diseases, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA
- Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA
| | - Patrick da Silva
- Ann Romney Center for Neurologic Diseases, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Rajesh K Krishnan
- Ann Romney Center for Neurologic Diseases, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Oleg Butovsky
- Ann Romney Center for Neurologic Diseases, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Laura M Cox
- Ann Romney Center for Neurologic Diseases, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.
| | - Howard L Weiner
- Ann Romney Center for Neurologic Diseases, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.
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10
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Goswami M, Bose PD. Gut microbial dysbiosis in the pathogenesis of leukemia: an immune-based perspective. Exp Hematol 2024; 133:104211. [PMID: 38527589 DOI: 10.1016/j.exphem.2024.104211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Revised: 03/04/2024] [Accepted: 03/16/2024] [Indexed: 03/27/2024]
Abstract
Leukemias are a set of clonal hematopoietic malignant diseases that develop in the bone marrow. Several factors influence leukemia development and progression. Among these, the gut microbiota is a major factor influencing a wide array of its processes. The gut microbial composition is linked to the risk of tumor development and the host's ability to respond to treatment, mostly due to the immune-modulatory effects of their metabolites. Despite such strong evidence, its role in the development of hematologic malignancies still requires attention of investigators worldwide. In this review, we make an effort to discuss the role of host gut microbiota-immune crosstalk in leukemia development and progression. Additionally, we highlight certain recently developed strategies to modify the gut microbial composition that may help to overcome dysbiosis in leukemia patients in the near future.
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Affiliation(s)
- Mayuri Goswami
- Department of Molecular Biology and Biotechnology, Cotton University, Panbazar, Guwahati, Assam, India
| | - Purabi Deka Bose
- Department of Molecular Biology and Biotechnology, Cotton University, Panbazar, Guwahati, Assam, India.
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11
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Pither MD, Andretta E, Rocca G, Balzarini F, Matamoros-Recio A, Colicchio R, Salvatore P, van Kooyk Y, Silipo A, Granucci F, Martin-Santamaria S, Chiodo F, Molinaro A, Di Lorenzo F. Deciphering the Chemical Language of the Immunomodulatory Properties of Veillonella parvula Lipopolysaccharide. Angew Chem Int Ed Engl 2024; 63:e202401541. [PMID: 38393988 DOI: 10.1002/anie.202401541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Revised: 02/22/2024] [Accepted: 02/23/2024] [Indexed: 02/25/2024]
Abstract
Veillonella parvula, prototypical member of the oral and gut microbiota, is at times commensal yet also potentially pathogenic. The definition of the molecular basis tailoring this contrasting behavior is key for broadening our understanding of the microbiota-driven pathogenic and/or tolerogenic mechanisms that take place within our body. In this study, we focused on the chemistry of the main constituent of the outer membrane of V. parvula, the lipopolysaccharide (LPS). LPS molecules indeed elicit pro-inflammatory and immunomodulatory responses depending on their chemical structures. Herein we report the structural elucidation of the LPS from two strains of V. parvula and show important and unprecedented differences in both the lipid and carbohydrate moieties, including the identification of a novel galactofuranose and mannitol-containing O-antigen repeating unit for one of the two strains. Furthermore, by harnessing computational studies, in vitro human cell models, as well as lectin binding solid-phase assays, we discovered that the two chemically diverse LPS immunologically behave differently and have attempted to identify the molecular determinant(s) governing this phenomenon. Whereas pro-inflammatory potential has been evidenced for the lipid A moiety, by contrast a plausible "immune modulating" action has been proposed for the peculiar O-antigen portion.
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Affiliation(s)
- Molly Dorothy Pither
- Department of Chemical Sciences, University of Naples Federico II, via Cinthia, 4, 80126, Naples, Italy
| | - Emanuela Andretta
- Department of Chemical Sciences, University of Naples Federico II, via Cinthia, 4, 80126, Naples, Italy
| | - Giuseppe Rocca
- Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza dell'Ateneo Nuovo, 1, 20126, Milan, Italy
| | - Fabio Balzarini
- Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Vrije Universiteit Amsterdam, 1007 MB, Amsterdam, The Netherlands
| | - Alejandra Matamoros-Recio
- Department of Structural and Chemical Biology, Centro de Investigaciones Biológicas, CIB-CSIC, C/ Ramiro de Maeztu, 9, 28040, Madrid, Spain
| | - Roberta Colicchio
- Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via Pansini, 5, 80131, Naples, Italy
| | - Paola Salvatore
- Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via Pansini, 5, 80131, Naples, Italy
| | - Yvette van Kooyk
- Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Vrije Universiteit Amsterdam, 1007 MB, Amsterdam, The Netherlands
| | - Alba Silipo
- Department of Chemical Sciences, University of Naples Federico II, via Cinthia, 4, 80126, Naples, Italy
| | - Francesca Granucci
- Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza dell'Ateneo Nuovo, 1, 20126, Milan, Italy
| | - Sonsoles Martin-Santamaria
- Department of Structural and Chemical Biology, Centro de Investigaciones Biológicas, CIB-CSIC, C/ Ramiro de Maeztu, 9, 28040, Madrid, Spain
| | - Fabrizio Chiodo
- Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Vrije Universiteit Amsterdam, 1007 MB, Amsterdam, The Netherlands
- Institute of Biomolecular Chemistry, National Research Council (CNR), Via Campi Flegrei, 34, 80078, Pozzuoli, Naples, Italy
| | - Antonio Molinaro
- Department of Chemical Sciences, University of Naples Federico II, via Cinthia, 4, 80126, Naples, Italy
| | - Flaviana Di Lorenzo
- Department of Chemical Sciences, University of Naples Federico II, via Cinthia, 4, 80126, Naples, Italy
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12
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Xu ZF, Yuan L, Zhang Y, Zhang W, Wei C, Wang W, Zhao D, Zhou D, Li J. The Gut Microbiome Correlated to Chemotherapy Efficacy in Diffuse Large B-Cell Lymphoma Patients. Hematol Rep 2024; 16:63-75. [PMID: 38390939 PMCID: PMC10885071 DOI: 10.3390/hematolrep16010007] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 08/10/2023] [Accepted: 12/29/2023] [Indexed: 02/24/2024] Open
Abstract
The gut microbiome (GMB) has been extensively reported to be associated with the development and prognosis of human diseases. This study aims to investigate the relationship between GMB composition and chemotherapy efficacy in diffuse large B-cell lymphoma (DLBCL). We demonstrated that DLBCL patients at diagnosis have altered GMB compositions. Significant enrichment of the Proteobacteria phylum in DLBCL patients was observed. Gene analysis showed a high abundance of virulence factors genes. We found baseline GMB to be associated with clinical outcomes. The emergence of Lactobacillus fermentum was correlated with better treatment outcome. Our pilot results suggested a correlation between GMB composition and DLBCL development and prognosis. Clues from our study, together with previous research, provided a rational foundation for further investigation on the pathogenesis, prognosis value, and targeted therapy of GMB in DLBCL.
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Affiliation(s)
- Zhuo-Fan Xu
- Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing 100005, China
- School of Medicine, Tsinghua University, Beijing 100084, China
| | - Li Yuan
- Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing 100005, China
| | - Yan Zhang
- Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing 100005, China
| | - Wei Zhang
- Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing 100005, China
| | - Chong Wei
- Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing 100005, China
| | - Wei Wang
- Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing 100005, China
| | - Danqing Zhao
- Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing 100005, China
| | - Daobin Zhou
- Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing 100005, China
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing 100005, China
| | - Jingnan Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing 100005, China
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13
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Feng Y, Chen S, Song Y, Liu S, Duan Y, Cai M, Kong T, Zhang H. A novel Sagittaria sagittifolia L. polysaccharides mitigate DSS-induced colitis via modulation of gut microbiota and MAPK/NF-κB signaling pathways. Int J Biol Macromol 2024; 254:127835. [PMID: 37924911 DOI: 10.1016/j.ijbiomac.2023.127835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Revised: 10/07/2023] [Accepted: 10/30/2023] [Indexed: 11/06/2023]
Abstract
Sagittaria sagittifolia L. polysaccharides possess anti-inflammatory, antioxidant, and immune-modulatory properties. In this study, we identified a novel S. sagittifolia L. polysaccharide, named PSSP-1, and evaluated its potential in alleviating dextran sulfate sodium (DSS)-induced colitis in a mouse model. The results demonstrated that administration of PSSP-1 at doses of 100, 200, and 400 mg/kg·bw significantly reduced the disease activity index (DAI) and suppressed the expression of inflammatory cytokines in UC mice. Furthermore, PSSP-1 treatment upregulated the expression levels of claudin-1, occludin, and ZO-1, and promoted the diversity and abundance of beneficial gut microbiota, including Lactobacillus and Candidatus_Saccharimonas, while reducing the levels of Bacteroidetes and Verrucomicrobiota. Particularly, the Lactobacillus_johnsonii species may play a potentially significant role in modulating colitis. Subsequently, there was a significant increase in the levels of short-chain fatty acids (SCFAs). Additionally, the correlation analyses revealed positive associations between PSSP-1 supplementation and Nitrosospira and Dialister, which are implicated in gut inflammation. Mechanistically, PSSP-1 intervention inhibited the protein phosphorylation of key molecules in the MAPK and NF-κB signaling pathways. Collectively, these findings suggest that PSSP-1 mitigates colitis symptoms by repairing the intestinal barrier, promoting microbial metabolism, and regulating the gut microbiota-MAPK/NF-κB signaling pathways.
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Affiliation(s)
- Yuqin Feng
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China; Division of Bioresources and Biosciences, Faculty of Agriculture, Graduate School of Kyushu University, 744 Motooka, Fukuoka 819-0395, Japan
| | - Simeng Chen
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China
| | - Yating Song
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China
| | - Shuhan Liu
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China
| | - Yuqing Duan
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China; Institute of Food Physical Processing, Jiangsu University, Zhenjiang 212013, China.
| | - Meihong Cai
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China
| | - Tianyu Kong
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China
| | - Haihui Zhang
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China.
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14
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Todman H, Arya S, Baker M, Stekel DJ. A model of antibiotic resistance genes accumulation through lifetime exposure from food intake and antibiotic treatment. PLoS One 2023; 18:e0289941. [PMID: 37590256 PMCID: PMC10434901 DOI: 10.1371/journal.pone.0289941] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Accepted: 07/30/2023] [Indexed: 08/19/2023] Open
Abstract
Antimicrobial resistant bacterial infections represent one of the most serious contemporary global healthcare crises. Acquisition and spread of resistant infections can occur through community, hospitals, food, water or endogenous bacteria. Global efforts to reduce resistance have typically focussed on antibiotic use, hygiene and sanitation and drug discovery. However, resistance in endogenous infections, e.g. many urinary tract infections, can result from life-long acquisition and persistence of resistance genes in commensal microbial flora of individual patients, which is not normally considered. Here, using individual based Monte Carlo models calibrated using antibiotic use data and human gut resistomes, we show that the long-term increase in resistance in human gut microbiomes can be substantially lowered by reducing exposure to resistance genes found food and water, alongside reduced medical antibiotic use. Reduced dietary exposure is especially important during patient antibiotic treatment because of increased selection for resistance gene retention; inappropriate use of antibiotics can be directly harmful to the patient being treated for the same reason. We conclude that a holistic approach to antimicrobial resistance that additionally incorporates food production and dietary considerations will be more effective in reducing resistant infections than a purely medical-based approach.
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Affiliation(s)
- Henry Todman
- School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, Nottingham, United Kingdom
| | - Sankalp Arya
- School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, Nottingham, United Kingdom
| | - Michelle Baker
- School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, Nottingham, United Kingdom
| | - Dov Joseph Stekel
- School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, Nottingham, United Kingdom
- Department of Mathematics and Applied Mathematics, University of Johannesburg, Rossmore, South Africa
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15
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Wang Z, Poveda A, Zhang Q, Unione L, Overkleeft HS, van der Marel GA, Jesús JB, Codée JDC. Total Synthesis and Structural Studies of Zwitterionic Bacteroides fragilis Polysaccharide A1 Fragments. J Am Chem Soc 2023; 145:14052-14063. [PMID: 37310804 PMCID: PMC10311536 DOI: 10.1021/jacs.3c03976] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Indexed: 06/15/2023]
Abstract
Zwitterionic polysaccharides (ZPSs) are exceptional carbohydrates, carrying both positively charged amine groups and negatively charged carboxylates, that can be loaded onto MHC-II molecules to activate T cells. It remains enigmatic, however, how these polysaccharides bind to these receptors, and to understand the structural features responsible for this "peptide-like" behavior, well-defined ZPS fragments are required in sufficient quantity and quality. We here present the first total synthesis of Bacteroides fragilis PS A1 fragments encompassing up to 12 monosaccharides, representing three repeating units. Key to our successful syntheses has been the incorporation of a C-3,C-6-silylidene-bridged "ring-inverted" galactosamine building block that was designed to act as an apt nucleophile as well as a stereoselective glycosyl donor. Our stereoselective synthesis route is further characterized by a unique protecting group strategy, built on base-labile protecting groups, which has allowed the incorporation of an orthogonal alkyne functionalization handle. Detailed structural studies have revealed that the assembled oligosaccharides take up a bent structure, which translates into a left-handed helix for larger PS A1 polysaccharides, presenting the key positively charged amino groups to the outside of the helix. The availability of the fragments and the insight into their secondary structure will enable detailed interaction studies with binding proteins to unravel the mode of action of these unique oligosaccharides at the atomic level.
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Affiliation(s)
- Zhen Wang
- Leiden
Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands
- National
Research Centre for Carbohydrate Synthesis, Jiangxi Normal University, 99 Ziyang Avenue, Nanchang 330022, China
| | - Ana Poveda
- CIC
bioGUNE, Basque Research & Technology Alliance (BRTA), Bizkaia Technology Park, Building
800, 48162 Derio, Bizkaia, Spain
| | - Qingju Zhang
- Leiden
Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands
- National
Research Centre for Carbohydrate Synthesis, Jiangxi Normal University, 99 Ziyang Avenue, Nanchang 330022, China
| | - Luca Unione
- CIC
bioGUNE, Basque Research & Technology Alliance (BRTA), Bizkaia Technology Park, Building
800, 48162 Derio, Bizkaia, Spain
- Ikerbasque,
Basque Foundation for Science, Maria Diaz de Haro 3, 48013 Bilbao, Bizkaia, Spain
| | - Herman S. Overkleeft
- Leiden
Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands
| | | | - Jiménez-Barbero Jesús
- CIC
bioGUNE, Basque Research & Technology Alliance (BRTA), Bizkaia Technology Park, Building
800, 48162 Derio, Bizkaia, Spain
- Ikerbasque,
Basque Foundation for Science, Maria Diaz de Haro 3, 48013 Bilbao, Bizkaia, Spain
- Department
of Organic Chemistry II, Faculty of Science and Technology, University of the Basque Country, EHU-UPV, 48940 Leioa, Spain
- Centro de
Investigación Biomédica En Red de Enfermedades Respiratorias
(CIBERES), 28029 Madrid, Spain
| | - Jeroen D. C. Codée
- Leiden
Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands
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16
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Jati S, Mahata S, Das S, Chatterjee S, Mahata SK. Catestatin: Antimicrobial Functions and Potential Therapeutics. Pharmaceutics 2023; 15:1550. [PMID: 37242791 PMCID: PMC10220906 DOI: 10.3390/pharmaceutics15051550] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Revised: 05/09/2023] [Accepted: 05/14/2023] [Indexed: 05/28/2023] Open
Abstract
The rapid increase in drug-resistant and multidrug-resistant infections poses a serious challenge to antimicrobial therapies, and has created a global health crisis. Since antimicrobial peptides (AMPs) have escaped bacterial resistance throughout evolution, AMPs are a category of potential alternatives for antibiotic-resistant "superbugs". The Chromogranin A (CgA)-derived peptide Catestatin (CST: hCgA352-372; bCgA344-364) was initially identified in 1997 as an acute nicotinic-cholinergic antagonist. Subsequently, CST was established as a pleiotropic hormone. In 2005, it was reported that N-terminal 15 amino acids of bovine CST (bCST1-15 aka cateslytin) exert antibacterial, antifungal, and antiyeast effects without showing any hemolytic effects. In 2017, D-bCST1-15 (where L-amino acids were changed to D-amino acids) was shown to exert very effective antimicrobial effects against various bacterial strains. Beyond antimicrobial effects, D-bCST1-15 potentiated (additive/synergistic) antibacterial effects of cefotaxime, amoxicillin, and methicillin. Furthermore, D-bCST1-15 neither triggered bacterial resistance nor elicited cytokine release. The present review will highlight the antimicrobial effects of CST, bCST1-15 (aka cateslytin), D-bCST1-15, and human variants of CST (Gly364Ser-CST and Pro370Leu-CST); evolutionary conservation of CST in mammals; and their potential as a therapy for antibiotic-resistant "superbugs".
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Affiliation(s)
- Suborno Jati
- Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USA;
| | - Sumana Mahata
- Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA;
| | - Soumita Das
- Department of Biomedical and Nutritional Science, University of Massachusetts Lowell, Lowell, MA 01854, USA;
| | - Saurabh Chatterjee
- Department of Medicine, University of California Irvine, Irvine, CA 92697, USA;
| | - Sushil K. Mahata
- Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA;
- VA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161, USA
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17
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Micoli F, Romano MR, Carboni F, Adamo R, Berti F. Strengths and weaknesses of pneumococcal conjugate vaccines. Glycoconj J 2023; 40:135-148. [PMID: 36652051 PMCID: PMC10027807 DOI: 10.1007/s10719-023-10100-3] [Citation(s) in RCA: 32] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 11/24/2022] [Accepted: 01/09/2023] [Indexed: 01/19/2023]
Abstract
Multivalent vaccines addressing an increasing number of Streptococcus pneumoniae types (7-, 10-, 13-, 15-, 20-valent) have been licensed over the last 22 years. The use of polysaccharide-protein conjugate vaccines has been pivotal in reducing the incidence of invasive pneumococcal disease despite the emergence of non-vaccine serotypes. Notwithstanding its undoubtable success, some weaknesses have called for continuous improvement of pneumococcal vaccination. For instance, despite their inclusion in pneumococcal conjugate vaccines, there are challenges associated with some serotypes. In particular, Streptococcus pneumoniae type 3 remains a major cause of invasive pneumococcal disease in several countries.Here a deep revision of the strengths and weaknesses of the licensed pneumococcal conjugate vaccines and other vaccine candidates currently in clinical development is reported.
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18
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Rajput M, Momin T, Singh A, Banerjee S, Villasenor A, Sheldon J, Paudel P, Rajput R. Determining the association between gut microbiota and its metabolites with higher intestinal Immunoglobulin A response. Vet Anim Sci 2023; 19:100279. [PMID: 36533218 PMCID: PMC9755367 DOI: 10.1016/j.vas.2022.100279] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Immunoglobulin A (IgA) is one of the important and most abundant immunoglobulins which neutralize invading pathogens at mucosal sites. Gut microbial community and their metabolites which are responsible for higher IgA are poorly known. The current study was carried out to determine those microbial community and their metabolites. Twenty-two healthy, 26 days wean piglets were used in the study. After 10 days of weaning, piglets were divided into two groups. Group 1 with significantly higher fecal IgA while group 2 with significantly lower IgA concentrations from each other. Both groups were analyzed for the fecal inflammatory cytokine, fecal microbial community using 16S ribosomal sequencing, and microbial metabolites using GC-MS. Results showed that Firmicutes and Bacteroidetes constituted 90.56% of the microbiome population in the fecal matter of pigs with higher IgA concentration while pigs with lower fecal IgA had Firmicutes and Bacteroidetes abundance as of 95.56%. Pigs with higher IgA had significantly higher Bacteroidota and Desulfobacterota populations, while significantly lower Firmicutes and Firmicutes/ Bacteroidota ratio (p <0.05). Roughly at the species level, animals with higher fecal IgA concentration had significantly higher bacteria which are associated with gut inflammation and infectious such Prevotella spp and Lachnospiraceae AC2044. Pigs with higher IgA had comparatively lower short-chain fatty acid (SCFA) such as acetic acid, butyric, formic acid, isovaleric acid, and propionic acid which has been associated with gut immune tolerance and immune homeostasis.
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Affiliation(s)
- Mrigendra Rajput
- Department of Biology, University of Dayton, Dayton, OH, 45469, United States of America
| | - Tooba Momin
- Department of Biology, University of Dayton, Dayton, OH, 45469, United States of America
| | - Amit Singh
- Department of Biology, University of Dayton, Dayton, OH, 45469, United States of America
| | - Surya Banerjee
- Department of Biological Sciences, Arkansas Tech University Russellville, AR, 72801, United States of America
| | - Andrew Villasenor
- Department of Biology, University of Dayton, Dayton, OH, 45469, United States of America
| | - Jessica Sheldon
- Department of Biology, University of Dayton, Dayton, OH, 45469, United States of America
| | - Pratikshya Paudel
- Department of Biological Sciences, Arkansas Tech University Russellville, AR, 72801, United States of America
| | - Ravindra Rajput
- Department of Mathematics, Statistics and Computer Science, G. B. Pant University of Agriculture and Technology, Pantnagar, 263145, India
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19
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Wang Z, Gimeno A, Lete MG, Overkleeft HS, van der Marel GA, Chiodo F, Jiménez‐Barbero J, Codée JDC. Synthetic Zwitterionic Streptococcus pneumoniae Type 1 Oligosaccharides Carrying Labile O-Acetyl Esters. Angew Chem Int Ed Engl 2023; 62:e202211940. [PMID: 36350770 PMCID: PMC10107948 DOI: 10.1002/anie.202211940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Indexed: 11/11/2022]
Abstract
We herein report the first total synthesis of the Streptococcus pneumoniae serotype 1 (Sp1) oligosaccharide, a unique zwitterionic capsular polysaccharide carrying labile O-acetyl esters. The target oligosaccharides, featuring rare α-2,4-diamino-2,4,6-trideoxy galactose (AAT) and α-galacturonic acids, were assembled up to the 9-mer level, in a highly stereoselective manner using trisaccharide building blocks. The lability of the O-acetyl esters imposed a careful deprotection scheme to prevent migration and hydrolysis. The migration was investigated in detail at various pD values using NMR spectroscopy, to show that migration and hydrolysis of the C-3-O-acetyl esters readily takes place under neutral conditions. Structural investigation showed the oligomers to adopt a right-handed helical structure with the acetyl esters exposed on the periphery of the helix in close proximity of the neighboring AAT residues, thereby imposing conformational restrictions on the AATα1-4GalA(3OAc) glycosidic linkages, supporting the helical shape of the polysaccharide, that has been proposed to be critical for its unique biological activity.
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Affiliation(s)
- Zhen Wang
- Leiden Institute of ChemistryLeiden UniversityEinsteinweg 552333 CCLeiden (TheNetherlands
| | - Ana Gimeno
- CIC bioGUNEBizkaia Technology Park, Building 801A48170DerioSpain
| | - Marta G. Lete
- CIC bioGUNEBizkaia Technology Park, Building 801A48170DerioSpain
| | - Herman S. Overkleeft
- Leiden Institute of ChemistryLeiden UniversityEinsteinweg 552333 CCLeiden (TheNetherlands
| | | | - Fabrizio Chiodo
- Institute of Biomolecular ChemistryNational Research Council (CNR)Pozzuoli, NapoliItaly
- Amsterdam Infection and Immunity InstituteDepartment of Molecular Cell Biology and Immunology Amsterdam UMC, Location VUmc1007 MBAmsterdam (TheNetherlands
| | - Jesús Jiménez‐Barbero
- CIC bioGUNEBizkaia Technology Park, Building 801A48170DerioSpain
- IkerbasqueBasque Foundation for SciencePlaza Euskadi 548009Bilbao, BizkaiaSpain
- Department of Organic ChemistryII Faculty of Science and Technology, EHU-UPV48940LeioaSpain
- Centro de Investigación Biomédica En Red de Enfermedades RespiratoriasMadridSpain
| | - Jeroen D. C. Codée
- Leiden Institute of ChemistryLeiden UniversityEinsteinweg 552333 CCLeiden (TheNetherlands
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20
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Che Y, Fu S, Wang H, Suo J, Chen C, Pu D, Li C, Yang Y. Correlation of the Gut Microbiota and Antitumor Immune Responses Induced by a Human Papillomavirus Therapeutic Vaccine. ACS Infect Dis 2022; 8:2494-2504. [PMID: 36342280 DOI: 10.1021/acsinfecdis.2c00305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Human papillomavirus (HPV) is the most common sexually transmitted pathogen worldwide and the major risk factor for cervical cancer. According to our previous study, antitumor immune responses induced by a therapeutic vaccine based on HPV E7 peptide are highly variable among individuals. Many studies have demonstrated that the discrepancy in the gut microbiota is an important factor in the development and regulation of the immune system. Therefore, we performed a systematic comparative analysis of gut microbiota in two groups of mice with significant differences in antitumor effects induced by the vaccine, as well as the correlation between immune cells and gut microbiota. We divided the mice into group A, in which the tumor continued growing, and group B, in which the tumor volume was significantly reduced. In group B mice, the vaccination induced a stronger antitumor activity with significantly enhanced IFN-γ-producing CD4+ and CD8+ T lymphocytes, as well as decreased immunosuppressive cells. A detailed gut microbiota analysis revealed a positive Spearman correlation between the percentage of CD8+ T cells and the relative abundance of Corynebacteriales, Parabacteroides, and Bacteroides_sp. Furthermore, the percentage of CD4+ and CD8+ T cells negatively correlated with the abundance of Proteobacteria and Bilophila. By contrast, the abundance of Proteobacteria, Desulfovibrio, and Bilophila positively correlated with the percentage of myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), and type 2-polarized tumor-associated macrophages (M2-TAMs). Overall, the composition of gut microbiota is related to vaccine-induced antitumor effects, and there is a correlation between some gut bacteria and vaccine-induced immune responses.
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Affiliation(s)
- Yuxin Che
- Department of Microbiology and Parasitology, College of Basic Medical Science, China Medical University, Shenyang 110122, China.,Department of Biochemistry & Molecular Biology, Shanxi Medical University, Taiyuan 030001, China
| | - Shihan Fu
- International School, Beijing University of Posts and Telecommunications, Beijing 100876, China
| | - Huan Wang
- Nursing College, Jinzhou Medical University, Jinzhou 121001, China
| | - Jinguo Suo
- Department of Microbiology and Parasitology, College of Basic Medical Science, China Medical University, Shenyang 110122, China
| | - Chunyan Chen
- Department of Microbiology and Parasitology, College of Basic Medical Science, China Medical University, Shenyang 110122, China
| | - Dan Pu
- Department of Microbiology and Parasitology, College of Basic Medical Science, China Medical University, Shenyang 110122, China
| | - Can Li
- Department of Microbiology and Parasitology, College of Basic Medical Science, China Medical University, Shenyang 110122, China
| | - Yang Yang
- Department of Microbiology and Parasitology, College of Basic Medical Science, China Medical University, Shenyang 110122, China
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Nawaz K, Cziesielski MJ, Mariappan KG, Cui G, Aranda M. Histone modifications and DNA methylation act cooperatively in regulating symbiosis genes in the sea anemone Aiptasia. BMC Biol 2022; 20:265. [DOI: 10.1186/s12915-022-01469-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Accepted: 11/17/2022] [Indexed: 12/03/2022] Open
Abstract
Abstract
Background
The symbiotic relationship between cnidarians and dinoflagellates is one of the most widespread endosymbiosis in our oceans and provides the ecological basis of coral reef ecosystems. Although many studies have been undertaken to unravel the molecular mechanisms underlying these symbioses, we still know little about the epigenetic mechanisms that control the transcriptional responses to symbiosis.
Results
Here, we used the model organism Exaiptasia diaphana to study the genome-wide patterns and putative functions of the histone modifications H3K27ac, H3K4me3, H3K9ac, H3K36me3, and H3K27me3 in symbiosis. While we find that their functions are generally conserved, we observed that colocalization of more than one modification and or DNA methylation correlated with significantly higher gene expression, suggesting a cooperative action of histone modifications and DNA methylation in promoting gene expression. Analysis of symbiosis genes revealed that activating histone modifications predominantly associated with symbiosis-induced genes involved in glucose metabolism, nitrogen transport, amino acid biosynthesis, and organism growth while symbiosis-suppressed genes were involved in catabolic processes.
Conclusions
Our results provide new insights into the mechanisms of prominent histone modifications and their interaction with DNA methylation in regulating symbiosis in cnidarians.
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22
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Chai L, Jabbie IS, Chen A, Jiang L, Li M, Rao H. Effects of waterborne Pb/Cu mixture on Chinese toad, Bufo gargarizans tadpoles: morphological, histological, and intestinal microbiota assessment. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2022; 29:90656-90670. [PMID: 35871197 DOI: 10.1007/s11356-022-22143-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Accepted: 07/18/2022] [Indexed: 06/15/2023]
Abstract
Coexistence of heavy metals in aquatic environments exert complex effects on amphibians. Here, the adverse effects of Pb (0.14 μM) combined with Cu at concentrations of 0, 0.25, and 1.0 μM were investigated in Bufo gargarizans tadpoles. Tadpoles were chronically exposed from Gosner stage (Gs) 26 to Gs 38, and morphology of tadpoles as well as intestinal histology and bacterial community were assessed. Our results indicated that Pb+Cu1.0 exposure induced significant retardation of somatic mass, total length, intestine mass, and intestine length as well as intestinal histological alterations. Pb+Cu0.25 and Pb+Cu1.0 exposure were associated with the loss of gut bacterial diversity. Proteobacteria and Bacteroidetes were two dominant phyla in tadpoles independently of heavy metal exposure, but the abundance of Proteobacteria increased significantly in Pb+Cu1.0 group and Bacteroidetes decreased significantly in all treatment groups. Furthermore, functional prediction indicated that metabolic disorders were associated with Pb+Cu0.25 and Pb+Cu1.0 exposure. Overall, relative limited shifts in intestinal bacterial diversity, composition, and functionality caused by Pb+Cu0 exposure, while coexistence of Pb and Cu induced gut dysbiosis and might further cause disturbance of metabolic homeostasis. The findings of this study provide insights into the effects of Pb and Cu coexistence on the health of amphibians.
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Affiliation(s)
- Lihong Chai
- School of Water and Environment, Chang'an University, Xi'an, 710054, People's Republic of China.
- Key Laboratory of Subsurface Hydrology and Ecological Effect in Arid Region of Ministry of Education, Chang'an University, Xi'an, 710054, China.
| | - Ibrahim Sory Jabbie
- School of Water and Environment, Chang'an University, Xi'an, 710054, People's Republic of China
- Key Laboratory of Subsurface Hydrology and Ecological Effect in Arid Region of Ministry of Education, Chang'an University, Xi'an, 710054, China
| | - Aixia Chen
- School of Water and Environment, Chang'an University, Xi'an, 710054, People's Republic of China
- Key Laboratory of Subsurface Hydrology and Ecological Effect in Arid Region of Ministry of Education, Chang'an University, Xi'an, 710054, China
| | - Ling Jiang
- School of Water and Environment, Chang'an University, Xi'an, 710054, People's Republic of China
- Key Laboratory of Subsurface Hydrology and Ecological Effect in Arid Region of Ministry of Education, Chang'an University, Xi'an, 710054, China
| | - Mengfan Li
- School of Water and Environment, Chang'an University, Xi'an, 710054, People's Republic of China
- Key Laboratory of Subsurface Hydrology and Ecological Effect in Arid Region of Ministry of Education, Chang'an University, Xi'an, 710054, China
| | - Huihui Rao
- School of Water and Environment, Chang'an University, Xi'an, 710054, People's Republic of China
- Key Laboratory of Subsurface Hydrology and Ecological Effect in Arid Region of Ministry of Education, Chang'an University, Xi'an, 710054, China
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The Species of Gut Bacteria Associated with Antitumor Immunity in Cancer Therapy. Cells 2022; 11:cells11223684. [PMID: 36429112 PMCID: PMC9688644 DOI: 10.3390/cells11223684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2022] [Revised: 10/30/2022] [Accepted: 11/16/2022] [Indexed: 11/22/2022] Open
Abstract
Both preclinical and clinical studies have demonstrated that the modulation of gut microbiota could be a promising strategy for enhancing antitumor immune responses and reducing resistance to immunotherapy in cancer. Various mechanisms, including activation of pattern recognition receptors, gut commensals-produced metabolites and antigen mimicry, have been revealed. Different gut microbiota modulation strategies have been raised, such as fecal microbiota transplantation, probiotics, and dietary selection. However, the identification of gut bacteria species that are either favorable or unfavorable for cancer therapy remains a major challenge. Herein, we summarized the findings related to gut microbiota species observed in the modulation of antitumor immunity. We also discussed the different mechanisms underlying different gut bacteria's functions and the potential applications of these bacteria to cancer immunotherapy in the future.
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Hao J, Wang S, Yang J, Zhang Q, Wu Z, Zhang D, Li A. Attenuated Streptococcus agalactiae WC1535 ∆Sia perturbs the gut microbiota of Oreochromis niloticus, massively colonizes the intestine, and induces intestinal mucosal immunity after intraperitoneal inoculation. Front Microbiol 2022; 13:1036432. [DOI: 10.3389/fmicb.2022.1036432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Accepted: 10/14/2022] [Indexed: 11/12/2022] Open
Abstract
We previously developed and assessed the effectiveness of the attenuated Streptococcus agalactiae (Group B Streptococcus, GBS) strain WC1535 ∆Sia (with neuA-D gene cluster deletion) vaccine in tilapia (Oreochromis niloticus). In this study, we characterized the bacterial communities of the tilapia intestines by 16S rRNA high-throughput sequencing and assessed the serum antibody response, expression of immune-related genes, and histological changes following formalin-killed GBS vaccine (FKV) and the live attenuated vaccine ∆Sia (LAV). Results showed that FKV and LAV induced robust systemic and intestinal mucosal immune responses in tilapia without causing obvious pathological changes in the hindgut, spleen, and head kidney but exerted different effects on intestinal bacterial communities. The richness or diversity of the intestinal bacterial community of FKV tilapia showed no significant changes compared with that of the control fish (p > 0.05) at either day 21 post-initial vaccination (21 dpiv) or day 35 (day 14 after the second immunization) (35 dpiv). The community composition of FKV tilapia and controls was significantly similar, although the relative abundance of some genera was significantly altered. Relative to control fish, the gut ecosystem of LAV tilapia was significantly disturbed with a substantial increase in community diversity at 21 dpiv (p < 0.05) and a significant decrease at 35 dpiv in fish with high serum antibody response (ΔSia35H) (p < 0.05). However, there was no significant difference between ΔSia35H and ΔSia35L (low serum antibody response) fish (p > 0.05). Moreover, the community composition of LAV tilapia at 21 dpiv or 35 dpiv was considerably different from that of the controls. Particularly, GBS ∆Sia was found to be abundant in the intestine at 21 and 35 dpiv. This result suggested that the parenteral administration of the LAV (∆Sia) may also have the effect of oral vaccination in addition to the immune effect of injection vaccination. In addition, a significant correlation was found between the expression of immune-related genes and certain bacterial species in the intestinal mucosal flora. Our findings will contribute to a better understanding of the effects of inactivated and attenuated vaccines on gut microbiota and their relationship with the immune response.
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The production and application of bacterial exopolysaccharides as biomaterials for bone regeneration. Carbohydr Polym 2022; 291:119550. [DOI: 10.1016/j.carbpol.2022.119550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 04/19/2022] [Accepted: 04/26/2022] [Indexed: 11/18/2022]
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Li J, Feng S, Yu L, Zhao J, Tian F, Chen W, Zhai Q. Capsular polysaccarides of probiotics and their immunomodulatory roles. FOOD SCIENCE AND HUMAN WELLNESS 2022. [DOI: 10.1016/j.fshw.2022.04.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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27
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Elahi N, Elahi H, Navashenaq JG, Abdollahzad H, Mahaki B, Soleimani D, Mostafaei R, Samadi M, Bagheri A, Nachvak SM. The Relationship between Major Dietary Patterns and Disease Activity of Rheumatoid Arthritis. Clin Nutr ESPEN 2022; 51:274-279. [PMID: 36184215 DOI: 10.1016/j.clnesp.2022.08.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Revised: 06/08/2022] [Accepted: 08/13/2022] [Indexed: 11/26/2022]
Abstract
AIM Rheumatoid arthritis is an inflammatory illness characterized by persistent and systemic inflammation. There is just a little amount of research on nutrition and RA progression. The goal of this research is to see whether there's a link between main eating trends and RA activity. METHODS In Kermanshah, Iran, 183 individuals with RA were studied in cross-sectional research. The American College of Rheumatology's 2010 criteria were used to diagnose RA. The disease activity score 28 and nutritional information from a reliable 147-item food frequency questionnaire were used to assess RA activity. Factor analysis was used to extract dietary patterns. RESULTS The researchers discovered three main eating trends, which they named. Individuals in the highest tertile of a high protein anti-inflammatory dietary pattern that emphasizes consumption of dairy products, red meats, white meats, vegetables oils, condiments, vegetables and fruits as well as low in salts and refined grain had lower DAS-28 scores than those in the first tertiles (T3 = 2.09 ± 0.14 vs. T1 = 3.75 ± 0.13; P-value = 0.001) after controlling for potential confounders. Patients in the top tertile of the low fiber dietary pattern had higher DAS-28 scores than those in the bottom tertile (T3 = 3.40 ± 0.15 vs. T1 = 2.95 ± 0.15; P-value = 0.036) than those in the bottom tertile. CONCLUSION This research found an inverse connection between RA activity and adopting a high-protein anti-inflammatory dietary pattern. Furthermore, adopting a low-fiber dietary pattern may be linked to increased RA disease activity. To confirm such a relationship, further research is needed in the future.
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Kaplonek P, Seeberger PH. Glycan Microarrays Containing Synthetic Streptococcus pneumoniae CPS Fragments and Their Application to Vaccine Development. METHODS IN MOLECULAR BIOLOGY (CLIFTON, N.J.) 2022; 2460:193-206. [PMID: 34972938 DOI: 10.1007/978-1-0716-2148-6_12] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Streptococcus pneumoniae is the leading source of life-endangering diseases like pneumonia, septicemia, and meningitis, as well as a major cause of death in children under 5 years old in developing countries. At least 98 serotypes of S. pneumoniae can be distinguished based on their structurally distinct capsular polysaccharides (CPS). Currently available CPS-based pneumococcal vaccines contain serotypes most frequently associated with invasive pneumococcal diseases. The polysaccharides used in commercial conjugate-vaccines are isolated from bacteria cultures comprising many laborious and operationally challenging steps followed by depolymerization of long polysaccharides into small fragments and their conjugation to the carrier protein. The medicinal chemistry approach for glycoconjugate vaccine development offers an exciting alternative to CPS isolation for a broad range of different glycan antigens. Glycan arrays containing well-defined synthetic glycans of CPS fragments and repeating units are used as a platform for the high-throughput screening of various serum samples and identification of protective glycotopes for vaccine candidates.
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Affiliation(s)
- Paulina Kaplonek
- Department of Biomolecular Systems, Max-Planck-Institute of Colloids and Interfaces, Potsdam, Germany
- Institute of Chemistry and Biochemistry, Freie Universitat Berlin, Berlin, Germany
| | - Peter H Seeberger
- Department of Biomolecular Systems, Max-Planck-Institute of Colloids and Interfaces, Potsdam, Germany.
- Institute of Chemistry and Biochemistry, Freie Universitat Berlin, Berlin, Germany.
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Reduced Virulence and Enhanced Host Adaption during Antibiotics Therapy: a Story of a Within-Host Carbapenem-Resistant Klebsiella pneumoniae Sequence Type 11 Evolution in a Patient with a Serious Scrotal Abscess. mSystems 2022; 7:e0134221. [PMID: 35196132 PMCID: PMC9040587 DOI: 10.1128/msystems.01342-21] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Carbapenem-resistant Klebsiella pneumoniae (CRKP) has disseminated globally and threatened human life. The sequence type (ST) 11 CRKP is a dominant clone in Asia, but how this clone evolves in vivo then adapts to the host and facilitates dissemination remains largely unknown. Here, the genomic dynamics of 4 ST11-CRKP isolates, which were sequentially collected from the urine of a patient with initial serious scrotal abscess and finally recovered without effective medication, were analyzed. Genomic differences were identified and their implications for pathogenesis and host adaptation were investigated. The related transcriptional pathways were further explored by RNA-Seq. Genomic analysis identified 4 to 24 mutations, among which 94% to 100% of them were synonymous or intergenic mutations. During 47 days of antibiotics therapy, CRKP underwent adaptive evolution, including tigecycline resistance and virulence attenuation. Tigecycline resistance was caused by a deletion within the ramR ribosomal binding site, which has been described by us previously. On the other hand, mutations associated with two genes, acyltransferase (act) and ompK26, resulted in the attenuation phenotype of ST11-CRKP. act deficiency reduced the capsular polysaccharide (CPS) production, enhanced biofilm formation, weakened capsular protection, and decreased induction of proinflammatory cytokines. Further RNA-Seq analysis revealed that act influenced the expression of ldhA, bglX, mtnK, and metE which likely participate in capsular synthesis and biofilm formation. ompK26 affected the virulence by its overexpression caused by the deletion of the upstream repressor binding site. This study presents a within-host adaption of ST11-CRKP and suggests an important role of CPS in the adaptive evolution of virulence and persistence of CRKP. IMPORTANCE Carbapenem-resistant Klebsiella pneumoniae (CRKP) has disseminated worldwide and can cause life-threatening infections, including pneumonia, bloodstream infections, urinary tract infections, intraabdominal infection, liver abscess, and meningitis. CRKP infection is the leading cause of high mortality in hospitals. The sequence type (ST) 11 CRKP is a dominant clone and accounts for 60% of CRKP infections in China. Recently, the ST11-CRKP with high transmissibility is increasingly identified. Understanding how this clone has evolved is crucial for developing strategies to control its further dissemination. The significance of our research is the identification of the in vivo genomic dynamics of ST11-CRKP and the genetic basis for ST11-CRKP that facilitate persistence and dissemination. Furthermore, our study also highlights the importance of monitoring the within-host evolution of pathogens during the treatment and developing interventions to minimize the potential impact of host adaptation on human health.
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Zierep PF, Vita R, Blazeska N, Moumbock AFA, Greenbaum JA, Peters B, Günther S. Towards the prediction of non-peptidic epitopes. PLoS Comput Biol 2022; 18:e1009151. [PMID: 35180214 PMCID: PMC8893639 DOI: 10.1371/journal.pcbi.1009151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Revised: 03/03/2022] [Accepted: 01/23/2022] [Indexed: 11/19/2022] Open
Abstract
In-silico methods for the prediction of epitopes can support and improve workflows for vaccine design, antibody production, and disease therapy. So far, the scope of B cell and T cell epitope prediction has been directed exclusively towards peptidic antigens. Nevertheless, various non-peptidic molecular classes can be recognized by immune cells. These compounds have not been systematically studied yet, and prediction approaches are lacking. The ability to predict the epitope activity of non-peptidic compounds could have vast implications; for example, for immunogenic risk assessment of the vast number of drugs and other xenobiotics. Here we present the first general attempt to predict the epitope activity of non-peptidic compounds using the Immune Epitope Database (IEDB) as a source for positive samples. The molecules stored in the Chemical Entities of Biological Interest (ChEBI) database were chosen as background samples. The molecules were clustered into eight homogeneous molecular groups, and classifiers were built for each cluster with the aim of separating the epitopes from the background. Different molecular feature encoding schemes and machine learning models were compared against each other. For those models where a high performance could be achieved based on simple decision rules, the molecular features were then further investigated. Additionally, the findings were used to build a web server that allows for the immunogenic investigation of non-peptidic molecules (http://tools-staging.iedb.org/np_epitope_predictor). The prediction quality was tested with samples from independent evaluation datasets, and the implemented method received noteworthy Receiver Operating Characteristic-Area Under Curve (ROC-AUC) values, ranging from 0.69–0.96 depending on the molecule cluster. Small molecules found in cosmetics, foodstuffs, dyes, and industrial materials, but also those produced by plants, bacteria, and animals can trigger strong reactions of the human immune system and can therefore be hazardous to health. In the present work, several thousand immune-reactive small molecules (so-called non-peptidic epitopes) were classified by molecular structure and studied with the aim of identifying specific parts of the molecules responsible for such immune responses. Using a machine-learning approach (random forests and neural networks), we identified some substructures that appear strikingly often in non-peptidic epitopes and which may be responsible for the hazardous immune response. Such knowledge may help to explain allergic reactions to chemicals and also to minimize the health risks of new chemicals in industrial production. To support this endeavor, we have implemented the method in a publicly available web application. This can be used for the prediction and identification of non-peptidic epitopes and their underlying substructures.
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Affiliation(s)
- Paul F. Zierep
- Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany
| | - Randi Vita
- Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, California, United States of America
| | - Nina Blazeska
- Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, California, United States of America
| | - Aurélien F. A. Moumbock
- Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany
| | - Jason A. Greenbaum
- Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, California, United States of America
| | - Bjoern Peters
- Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, California, United States of America
- * E-mail: (BP); (SG)
| | - Stefan Günther
- Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany
- * E-mail: (BP); (SG)
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Polysaccharide hydrogels: Functionalization, construction and served as scaffold for tissue engineering. Carbohydr Polym 2022; 278:118952. [PMID: 34973769 DOI: 10.1016/j.carbpol.2021.118952] [Citation(s) in RCA: 117] [Impact Index Per Article: 39.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2021] [Revised: 11/07/2021] [Accepted: 11/26/2021] [Indexed: 02/07/2023]
Abstract
Polysaccharide hydrogels have been widely utilized in tissue engineering. They interact with the organismal environments, modulating the cargos release and realizing of long-term survival and activations of living cells. In this review, the potential strategies for modification of polysaccharides were introduced firstly. It is not only used to functionalize the polysaccharides for the consequent formation of hydrogels, but also used to introduce versatile side groups for the regulation of cell behavior. Then, techniques and underlying mechanisms in inducing the formation of hydrogels by polysaccharides or their derivatives are briefly summarized. Finally, the applications of polysaccharide hydrogels in vivo, mainly focus on the performance for alleviation of foreign-body response (FBR) and as cell scaffolds for tissue regeneration, are exemplified. In addition, the perspectives and challenges for further research are addressed. It aims to provide a comprehensive framework about the potentials and challenges that the polysaccharide hydrogels confronting in tissue engineering.
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Gorreja F, Walker WA. The potential role of adherence factors in probiotic function in the gastrointestinal tract of adults and pediatrics: a narrative review of experimental and human studies. Gut Microbes 2022; 14:2149214. [PMID: 36469568 PMCID: PMC9728474 DOI: 10.1080/19490976.2022.2149214] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Accepted: 11/15/2022] [Indexed: 12/12/2022] Open
Abstract
Numerous studies point to the important role of probiotic bacteria in gastrointestinal health. Probiotics act through mechanisms affecting enteric pathogens, epithelial barrier function, immune signaling, and conditioning of indigenous microbiota. Once administered, probiotics reach the gastrointestinal tract and interact with the host through bacterial surface molecules, here called adhesion factors, which are either strain- or specie-specific. Probiotic adhesion, through structural adhesion factors, is a mechanism that facilitates persistence within the gastrointestinal tract and triggers the initial host responses. Thus, an understanding of specific probiotic adhesion mechanisms could predict how specific probiotic strains elicit benefits and the potential of adherence factors as a proxy to predict probiotic function. This review summarizes the present understanding of probiotic adherence in the gastrointestinal tract. It highlights the bacterial adhesion structure types, their molecular communication with the host and the consequent impact on intestinal diseases in both adult and pediatric populations. Finally, we discuss knockout/isolation studies as direct evidence for adhesion factors conferring anti-inflammatory and pathogen inhibition properties to a probiotic.What is known: Probiotics can be used to treat clinical conditions.Probiotics improve dysbiosis and symptoms.Clinical trials may not confirm in vitro and animal studies.What is new: Adhesion structures may be important for probiotic function.Need to systematically determine physical characteristics of probiotics before selecting for clinical trials.Probiotics may be genetically engineered to add to clinical efficacy.
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Affiliation(s)
- Frida Gorreja
- Department of Microbiology and Immunology, Institute for Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Nutrition-Gut-Brain Interactions Research Centre, School of Medical Sciences, Örebro University, Örebro, Sweden
| | - W. Allan Walker
- Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children, Harvard Medical School, Boston, Massachusetts, USA
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Gut Bacteria and Neuropsychiatric Disorders. Microorganisms 2021; 9:microorganisms9122583. [PMID: 34946184 PMCID: PMC8708963 DOI: 10.3390/microorganisms9122583] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Revised: 11/23/2021] [Accepted: 11/26/2021] [Indexed: 12/11/2022] Open
Abstract
Bacteria in the gut microbiome plays an intrinsic part in immune activation, intestinal permeability, enteric reflex, and entero-endocrine signaling. Apart from physiological and structural changes brought about by gut bacteria on entero-epithelial cells and mucus layers, a vast number of signals generated in the gastro-intestinal tract (GIT) reaches the brain via the vagus nerve. Research on the gut–brain axis (GBA) has mostly been devoted to digestive functions and satiety. Less papers have been published on the role gut microbiota play in mood, cognitive behavior and neuropsychiatric disorders such as autism, depression and schizophrenia. Whether we will be able to fully decipher the connection between gut microbiota and mental health is debatable, especially since the gut microbiome is diverse, everchanging and highly responsive to external stimuli. Nevertheless, the more we discover about the gut microbiome and the more we learn about the GBA, the greater the chance of developing novel therapeutics, probiotics and psychobiotics to treat gastro-intestinal disorders such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), but also improve cognitive functions and prevent or treat mental disorders. In this review we focus on the influence gut bacteria and their metabolites have on neuropsychiatric disorders.
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Anish C, Beurret M, Poolman J. Combined effects of glycan chain length and linkage type on the immunogenicity of glycoconjugate vaccines. NPJ Vaccines 2021; 6:150. [PMID: 34893630 PMCID: PMC8664855 DOI: 10.1038/s41541-021-00409-1] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 11/01/2021] [Indexed: 11/09/2022] Open
Abstract
The development and use of antibacterial glycoconjugate vaccines have significantly reduced the occurrence of potentially fatal childhood and adult diseases such as bacteremia, bacterial meningitis, and pneumonia. In these vaccines, the covalent linkage of bacterial glycans to carrier proteins augments the immunogenicity of saccharide antigens by triggering T cell-dependent B cell responses, leading to high-affinity antibodies and durable protection. Licensed glycoconjugate vaccines either contain long-chain bacterial polysaccharides, medium-sized oligosaccharides, or short synthetic glycans. Here, we discuss factors that affect the glycan chain length in vaccines and review the available literature discussing the impact of glycan chain length on vaccine efficacy. Furthermore, we evaluate the available clinical data on licensed glycoconjugate vaccine preparations with varying chain lengths against two bacterial pathogens, Haemophilus influenzae type b and Neisseria meningitidis group C, regarding a possible correlation of glycan chain length with their efficacy. We find that long-chain glycans cross-linked to carrier proteins and medium-sized oligosaccharides end-linked to carriers both achieve high immunogenicity and efficacy. However, end-linked glycoconjugates that contain long untethered stretches of native glycan chains may induce hyporesponsiveness by T cell-independent activation of B cells, while cross-linked medium-sized oligosaccharides may suffer from suboptimal saccharide epitope accessibility.
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Affiliation(s)
- Chakkumkal Anish
- grid.497529.40000 0004 0625 7026Bacterial Vaccines Discovery and Early Development, Janssen Vaccines and Prevention B.V., Leiden, Netherlands
| | - Michel Beurret
- Bacterial Vaccines Discovery and Early Development, Janssen Vaccines and Prevention B.V., Leiden, Netherlands.
| | - Jan Poolman
- grid.497529.40000 0004 0625 7026Bacterial Vaccines Discovery and Early Development, Janssen Vaccines and Prevention B.V., Leiden, Netherlands
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35
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The influence of early-life microbial exposures on long-term respiratory health. Paediatr Respir Rev 2021; 40:15-23. [PMID: 34140238 DOI: 10.1016/j.prrv.2021.05.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Accepted: 05/20/2021] [Indexed: 11/21/2022]
Abstract
Host-microbiome interactions exert a profound influence on human physiology and health outcomes. In particular, certain characteristics of commensal microbiota during a critical period in early life are essential for the establishment of immune tone and metabolic control. An increasing body of evidence suggests that early life exposures that disrupt these interactions can substantially influence life-long risks for respiratory disease. Here, we explore how such early life exposures, including antibiotic exposure, maternal diet, preterm birth, mode of delivery, breastfeeding, and environmental variables shape the infant microbiome, and the mechanisms by such changes can in turn impact respiratory health.
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Stergiou N, Urschbach M, Gabba A, Schmitt E, Kunz H, Besenius P. The Development of Vaccines from Synthetic Tumor-Associated Mucin Glycopeptides and their Glycosylation-Dependent Immune Response. CHEM REC 2021; 21:3313-3331. [PMID: 34812564 DOI: 10.1002/tcr.202100182] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 10/31/2021] [Accepted: 11/02/2021] [Indexed: 12/15/2022]
Abstract
Tumor-associated carbohydrate antigens are overexpressed as altered-self in most common epithelial cancers. Their glycosylation patterns differ from those of healthy cells, functioning as an ID for cancer cells. Scientists have been developing anti-cancer vaccines based on mucin glycopeptides, yet the interplay of delivery system, adjuvant and tumor associated MUC epitopes in the induced immune response is not well understood. The current state of the art suggests that the identity, abundancy and location of the glycans on the MUC backbone are all key parameters in the cellular and humoral response. This review shares lessons learned by us in over two decades of research in glycopeptide vaccines. By bridging synthetic chemistry and immunology, we discuss efforts in designing synthetic MUC1/4/16 vaccines and focus on the role of glycosylation patterns. We provide a brief introduction into the mechanisms of the immune system and aim to promote the development of cancer subunit vaccines.
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Affiliation(s)
- Natascha Stergiou
- Radionuclide Center, Radiology and Nuclear medicine Amsterdam UMC, VU University, De Boelelaan 1085c, 1081 HV, Amsterdam, the Netherlands
| | - Moritz Urschbach
- Department of Chemistry, Johannes Gutenberg University Mainz, Duesbergweg 10-14, 55128, Mainz, Germany
| | - Adele Gabba
- Department of Chemistry, Johannes Gutenberg University Mainz, Duesbergweg 10-14, 55128, Mainz, Germany
| | - Edgar Schmitt
- Institute of Immunology, University Medical Center Mainz, Langenbeckstr. 1, 55131, Mainz, Germany
| | - Horst Kunz
- Department of Chemistry, Johannes Gutenberg University Mainz, Duesbergweg 10-14, 55128, Mainz, Germany
| | - Pol Besenius
- Department of Chemistry, Johannes Gutenberg University Mainz, Duesbergweg 10-14, 55128, Mainz, Germany
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37
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Puri K, Kulkarni SS. Total Synthesis of the Phosphorylated Zwitterionic Trisaccharide Repeating Unit of Photorhabdus temperata cinerea 3240. Org Lett 2021; 23:7083-7087. [PMID: 34459612 DOI: 10.1021/acs.orglett.1c02487] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Herein, we report the total synthesis of the phosphorylated zwitterionic trisaccharide repeating unit of Photorhabdus temperata subsp. cinerea 3240. The efficient route involves regio- and stereoselective assembly of trisaccharide with rare deoxyamino sugar AAT at the nonreducing end, late stage oxidation, and installation of a phosphate linker on the trisaccharide. The total synthesis was completed via a longest linear sequence of 24 steps in 6.5% overall yield.
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Affiliation(s)
- Krishna Puri
- Department of Chemistry, Indian Institute of Technology Bombay, Mumbai 400076, India
| | - Suvarn S Kulkarni
- Department of Chemistry, Indian Institute of Technology Bombay, Mumbai 400076, India
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38
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Abstract
Polysaccharides are often the most abundant antigens found on the extracellular surfaces of bacterial cells. These polysaccharides play key roles in interactions with the outside world, and for many bacterial pathogens, they represent what is presented to the human immune system. As a result, many vaccines have been or currently are being developed against carbohydrate antigens. In this review, we explore the diversity of capsular polysaccharides (CPS) in Salmonella and other selected bacterial species and explain the classification and function of CPS as vaccine antigens. Despite many vaccines being developed using carbohydrate antigens, the low immunogenicity and the diversity of infecting strains and serovars present an antigen formulation challenge to manufacturers. Vaccines tend to focus on common serovars or have changing formulations over time, reflecting the trends in human infection, which can be costly and time-consuming. We summarize the approaches to generate carbohydrate-based vaccines for Salmonella, describe vaccines that are in development and emphasize the need for an effective vaccine against non-typhoidal Salmonella strains.
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Abstract
Carbohydrates are the most abundant and one of the most important biomacromolecules in Nature. Except for energy-related compounds, carbohydrates can be roughly divided into two categories: Carbohydrates as matter and carbohydrates as information. As matter, carbohydrates are abundantly present in the extracellular matrix of animals and cell walls of various plants, bacteria, fungi, etc., serving as scaffolds. Some commonly found polysaccharides are featured as biocompatible materials with controllable rigidity and functionality, forming polymeric biomaterials which are widely used in drug delivery, tissue engineering, etc. As information, carbohydrates are usually referred to the glycans from glycoproteins, glycolipids, and proteoglycans, which bind to proteins or other carbohydrates, thereby meditating the cell-cell and cell-matrix interactions. These glycans could be simplified as synthetic glycopolymers, glycolipids, and glycoproteins, which could be afforded through polymerization, multistep synthesis, or a semisynthetic strategy. The information role of carbohydrates can be demonstrated not only as targeting reagents but also as immune antigens and adjuvants. The latter are also included in this review as they are always in a macromolecular formulation. In this review, we intend to provide a relatively comprehensive summary of carbohydrate-based macromolecular biomaterials since 2010 while emphasizing the fundamental understanding to guide the rational design of biomaterials. Carbohydrate-based macromolecules on the basis of their resources and chemical structures will be discussed, including naturally occurring polysaccharides, naturally derived synthetic polysaccharides, glycopolymers/glycodendrimers, supramolecular glycopolymers, and synthetic glycolipids/glycoproteins. Multiscale structure-function relationships in several major application areas, including delivery systems, tissue engineering, and immunology, will be detailed. We hope this review will provide valuable information for the development of carbohydrate-based macromolecular biomaterials and build a bridge between the carbohydrates as matter and the carbohydrates as information to promote new biomaterial design in the near future.
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Affiliation(s)
- Lu Su
- The State Key Laboratory of Molecular Engineering of Polymers and Department of Macromolecular Science, Fudan University, Shanghai 200433, China.,Institute for Complex Molecular Systems, Laboratory of Macromolecular and Organic Chemistry, Eindhoven University of Technology, Eindhoven 5600, The Netherlands
| | - Yingle Feng
- The State Key Laboratory of Molecular Engineering of Polymers and Department of Macromolecular Science, Fudan University, Shanghai 200433, China.,Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education and School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an, Shaanxi 710119, P. R. China
| | - Kongchang Wei
- Empa, Swiss Federal Laboratories for Materials Science and Technology, Department of Materials meet Life, Laboratory for Biomimetic Membranes and Textiles, Lerchenfeldstrasse 5, St. Gallen 9014, Switzerland
| | - Xuyang Xu
- The State Key Laboratory of Molecular Engineering of Polymers and Department of Macromolecular Science, Fudan University, Shanghai 200433, China
| | - Rongying Liu
- The State Key Laboratory of Molecular Engineering of Polymers and Department of Macromolecular Science, Fudan University, Shanghai 200433, China
| | - Guosong Chen
- The State Key Laboratory of Molecular Engineering of Polymers and Department of Macromolecular Science, Fudan University, Shanghai 200433, China.,Multiscale Research Institute of Complex Systems, Fudan University, Shanghai 200433, China
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40
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Hansen AK, Hansen CHF. The microbiome and rodent models of immune mediated diseases. Mamm Genome 2021; 32:251-262. [PMID: 33792799 PMCID: PMC8012743 DOI: 10.1007/s00335-021-09866-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Accepted: 03/12/2021] [Indexed: 02/07/2023]
Abstract
Over the last six decades production of laboratory rodents have been refined with the aim of eliminating all pathogens, which could influence research results. This has, however, also created rodents with little diversity in their microbiota. Until 10 years ago the impact of the microbiota on the outcome of rodent studies was ignored, but today it is clear that the phenotype of rodent models differs essentially in relation to the environment of origin, i.e. different breeders or different rooms. In this review, we outline the mechanisms behind gut bacterial impact on rodent models of immune mediated diseases, and how differences in environment of origin leads to phenotypic model differences within research areas such as infectious diseases and vaccine development, the metabolic syndrome, gut immunity and inflammation, autoimmunity and allergy. Finally, we sum up some tools to handle this impact to increase reproducibility and translatability of rodent models.
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Affiliation(s)
- Axel Kornerup Hansen
- Section of Experimental Animal Models, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 9, 1870, Frederiksberg C, Denmark.
| | - Camilla Hartmann Friis Hansen
- Section of Experimental Animal Models, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 9, 1870, Frederiksberg C, Denmark.
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41
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Li Y, Jiang N, Zhang W, Lv Z, Liu J, Shi H. Bacillus amyloliquefaciens- 9 Reduces Somatic Cell Count and Modifies Fecal Microbiota in Lactating Goats. Mar Drugs 2021; 19:md19080404. [PMID: 34436243 PMCID: PMC8400666 DOI: 10.3390/md19080404] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 07/10/2021] [Accepted: 07/17/2021] [Indexed: 12/15/2022] Open
Abstract
Subclinical mastitis is one of the major problems affecting dairy animals’ productivity and is classified based on milk somatic cell counts (SCC). Previous data showed that marine-derived Bacillus amyloliquefaciens-9 (GB-9) improved the immunity and the nonspecific immune defense system of the body. In this study, the potential role of GB-9 in improving subclinical mastitis was assessed with Radix Tetrastigmae (RT) as a positive control in subclinical mastitis Saanen dairy goats. The current data showed that GB-9 and RT significantly reduced the SCC in dairy goats. After being fed with GB-9 or RT, the decreased concentrations of malondialdehyde, IgA, IgM, IL-2, IL-4, and IL-6 were observed. The amplicon sequencing analysis of fecal samples revealed that GB-9 significantly altered the bacterial community. Bacteroides and Phascolarctobacterium were the major genera that respond to GB-9 feeding. The correlation analysis using weighted gene co-expression network analysis showed a MePink module was most associated with the serum concentrations of immunoglobulin and interleukin. The MePink module contained 89 OTUs. The feeding of GB-9 in decreasing the SCC was associated with the altered abundance of Bacteroides, which was correlated with the concentrations of immunoglobulins and chemokines. Collectively, the current data suggested that marine-derived GB-9 could be a helpful probiotic to control subclinical mastitis.
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Affiliation(s)
- Yongtao Li
- Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Institute of Dairy Science, College of Animal Sciences, Zhejiang University, Hangzhou 310015, China; (Y.L.); (N.J.); (W.Z.); (J.L.)
| | - Nannan Jiang
- Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Institute of Dairy Science, College of Animal Sciences, Zhejiang University, Hangzhou 310015, China; (Y.L.); (N.J.); (W.Z.); (J.L.)
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China;
| | - Wenying Zhang
- Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Institute of Dairy Science, College of Animal Sciences, Zhejiang University, Hangzhou 310015, China; (Y.L.); (N.J.); (W.Z.); (J.L.)
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China;
| | - Zhengbing Lv
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China;
| | - Jianxin Liu
- Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Institute of Dairy Science, College of Animal Sciences, Zhejiang University, Hangzhou 310015, China; (Y.L.); (N.J.); (W.Z.); (J.L.)
| | - Hengbo Shi
- Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Institute of Dairy Science, College of Animal Sciences, Zhejiang University, Hangzhou 310015, China; (Y.L.); (N.J.); (W.Z.); (J.L.)
- Correspondence:
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42
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Pathan EK, Ghosh B, Podilapu AR, Kulkarni SS. Total Synthesis of the Repeating Unit of Bacteroides fragilis Zwitterionic Polysaccharide A1. J Org Chem 2021; 86:6090-6099. [PMID: 33843231 DOI: 10.1021/acs.joc.0c02935] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Zwitterionic polysaccharides isolated from commensal bacteria are endowed with unique immunological properties and are emerging as immunotherapeutic agents as well as vaccine carriers. Reported herein is a total synthesis of the repeating unit of Bacteroides fragilis zwitterionic polysaccharide A1 (PS A1). The structurally complex tetrasaccharide unit contains a rare sugar 2-acetamido-4-amino-2,4,6-trideoxy-d-galactose (AAT) and two consecutive 1,2-cis glycosidic linkages. The repeating unit was efficiently assembled by rapid synthesis of d-galactosamine and AAT building blocks from cheap and abundant d-mannose via a one-pot SN2 displacement of 2,4-bistriflates and installation of all of the glycosidic bonds in a highly stereoselective manner. The total synthesis involves a longest linear sequence of 17 steps with 3.47% overall yield.
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Affiliation(s)
- Ennus K Pathan
- Department of Chemistry, Indian Institute of Technology Bombay, Mumbai 400076, India
| | - Bhaswati Ghosh
- Department of Chemistry, Indian Institute of Technology Bombay, Mumbai 400076, India
| | - Ananda Rao Podilapu
- Department of Chemistry, Indian Institute of Technology Bombay, Mumbai 400076, India
| | - Suvarn S Kulkarni
- Department of Chemistry, Indian Institute of Technology Bombay, Mumbai 400076, India
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43
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Abstract
Exposed surfaces of mammals are colonized with 100 trillion indigenous bacteria, fungi, and viruses, creating a diverse ecosystem known as the human microbiome. The gut microbiome is the richest microbiome and is now known to regulate postnatal skeletal development and the activity of the major endocrine regulators of bone. Parathyroid hormone (PTH) is one of the bone-regulating hormone that requires elements of the gut microbiome to exert both its bone catabolic and its bone anabolic effects. How the gut microbiome regulates the skeletal response to PTH is object of intense research. Involved mechanisms include absorption and diffusion of bacterial metabolites, such as short-chain fatty acids, and trafficking of immune cells from the gut to the bone marrow. This review will focus on how the gut microbiome communicates and regulates bone marrow cells in order to modulate the skeletal effects of PTH.
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Affiliation(s)
- Roberto Pacifici
- Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University, Atlanta, GA, USA
- Emory Microbiome Research Center, Emory University, Atlanta, GA, USA
- Immunology and Molecular Pathogenesis Program, Emory University, Atlanta, GA, USA
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44
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Liu ZX, Huang SL, Hou J, Guo XP, Wang FS, Sheng JZ. Cell-based high-throughput screening of polysaccharide biosynthesis hosts. Microb Cell Fact 2021; 20:62. [PMID: 33663495 PMCID: PMC7934428 DOI: 10.1186/s12934-021-01555-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Accepted: 02/26/2021] [Indexed: 02/05/2023] Open
Abstract
Valuable polysaccharides are usually produced using wild-type or metabolically-engineered host microbial strains through fermentation. These hosts act as cell factories that convert carbohydrates, such as monosaccharides or starch, into bioactive polysaccharides. It is desirable to develop effective in vivo high-throughput approaches to screen cells that display high-level synthesis of the desired polysaccharides. Uses of single or dual fluorophore labeling, fluorescence quenching, or biosensors are effective strategies for cell sorting of a library that can be applied during the domestication of industrial engineered strains and metabolic pathway optimization of polysaccharide synthesis in engineered cells. Meanwhile, high-throughput screening strategies using each individual whole cell as a sorting section are playing growing roles in the discovery and directed evolution of enzymes involved in polysaccharide biosynthesis, such as glycosyltransferases. These enzymes and their mutants are in high demand as tool catalysts for synthesis of saccharides in vitro and in vivo. This review provides an introduction to the methodologies of using cell-based high-throughput screening for desired polysaccharide-biosynthesizing cells, followed by a brief discussion of potential applications of these approaches in glycoengineering.
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Affiliation(s)
- Zi-Xu Liu
- Key Laboratory of Chemical Biology of Natural Products (Ministry of Education), Institute of Biochemical and Biotechnological Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China
| | - Si-Ling Huang
- Bloomage BioTechnology Corp., Ltd., Jinan, 250010, China
| | - Jin Hou
- The State Key Laboratory of Microbial Technology, Shandong University, Jinan, 250100, China
| | - Xue-Ping Guo
- Bloomage BioTechnology Corp., Ltd., Jinan, 250010, China
| | - Feng-Shan Wang
- Key Laboratory of Chemical Biology of Natural Products (Ministry of Education), Institute of Biochemical and Biotechnological Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China. .,National Glycoengineering Research Center, Shandong University, Jinan, 250012, China.
| | - Ju-Zheng Sheng
- Key Laboratory of Chemical Biology of Natural Products (Ministry of Education), Institute of Biochemical and Biotechnological Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China. .,National Glycoengineering Research Center, Shandong University, Jinan, 250012, China.
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45
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Bian S, Zeng W, Li Q, Li Y, Wong NK, Jiang M, Zuo L, Hu Q, Li L. Genetic Structure, Function, and Evolution of Capsule Biosynthesis Loci in Vibrio parahaemolyticus. Front Microbiol 2021; 11:546150. [PMID: 33505361 PMCID: PMC7829505 DOI: 10.3389/fmicb.2020.546150] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Accepted: 11/24/2020] [Indexed: 01/29/2023] Open
Abstract
Capsule-forming extracellular polysaccharides are crucial for bacterial host colonization, invasion, immune evasion, and ultimately pathogenicity. Due to warming ocean waters and human encroachment of coastal ecosystems, Vibrio parahaemolyticus has emerged as a globally important foodborne enteropathogen implicated in acute gastroenteritis, wound infections, and septic shock. Conventionally, the antigenic properties of lipopolysaccharide (LPS, O antigen) and capsular polysaccharide (CPS, K antigen) have provided a basis for serotyping V. parahaemolyticus, whereas disclosure of genetic elements encoding 13 O-serogroups have allowed molecular serotyping methods to be developed. However, the genetic structure of CPS loci for 71 K-serogroups has remained unidentified, limiting progress in understanding its roles in V. parahaemolyticus pathophysiology. In this study, we identified and characterized the genetic structure and their evolutionary relationship of CPS loci of 40 K-serogroups through whole genome sequencing of 443 V. parahaemolyticus strains. We found a distinct pattern of CPS gene cluster across different K-serogroups and expanded its new 3'-border by identifying glpX as a key gene conserved across all K-serogroups. A total of 217 genes involved in CPS biosynthesis were annotated. Functional contents and genetic structure of the 40 K-serogroups were analyzed. Based on inferences from species trees and gene trees, we proposed an evolution model of the CPS gene clusters of 40 K-serogroups. Horizontal gene transfer by recombination from other Vibrio species, gene duplication is likely to play instrumental roles in the evolution of CPS in V. parahaemolyticus. This is the first time, to the best of our knowledge, that a large scale of CPS gene clusters of different K-serogroups in V. parahaemolyticus have been identified and characterized in evolutionary contexts. This work should help advance understanding on the variation of CPS in V. parahaemolyticus and provide a framework for developing diagnostically relevant serotyping methods.
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Affiliation(s)
- Shengzhe Bian
- BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, China
- BGI-Shenzhen, Shenzhen, China
- Shenzhen Key Laboratory of Unknown Pathogen Identification, Shenzhen, China
- School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, China
| | - Wenhong Zeng
- Jiangxi University of Traditional Chinese Medicine, Nanchang, China
| | - Qiwen Li
- BGI-Shenzhen, Shenzhen, China
- Shenzhen Key Laboratory of Unknown Pathogen Identification, Shenzhen, China
| | - Yinghui Li
- Shenzhen Center for Disease Control and Prevention, Shenzhen, China
| | - Nai-Kei Wong
- National Clinical Research Center for Infectious Diseases, Shenzhen Third People’s Hospital, The Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, China
| | - Min Jiang
- Shenzhen Center for Disease Control and Prevention, Shenzhen, China
| | - Le Zuo
- Shenzhen Center for Disease Control and Prevention, Shenzhen, China
| | - Qinghua Hu
- Shenzhen Center for Disease Control and Prevention, Shenzhen, China
| | - Liqiang Li
- BGI-Shenzhen, Shenzhen, China
- Shenzhen Key Laboratory of Unknown Pathogen Identification, Shenzhen, China
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46
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Su T, Nakamoto R, Chun YY, Chua WZ, Chen JH, Zik JJ, Sham LT. Decoding capsule synthesis in Streptococcus pneumoniae. FEMS Microbiol Rev 2020; 45:6041728. [PMID: 33338218 DOI: 10.1093/femsre/fuaa067] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Accepted: 12/07/2020] [Indexed: 12/20/2022] Open
Abstract
Streptococcus pneumoniae synthesizes more than one hundred types of capsular polysaccharides (CPS). While the diversity of the enzymes and transporters involved is enormous, it is not limitless. In this review, we summarized the recent progress on elucidating the structure-function relationships of CPS, the mechanisms by which they are synthesized, how their synthesis is regulated, the host immune response against them, and the development of novel pneumococcal vaccines. Based on the genetic and structural information available, we generated provisional models of the CPS repeating units that remain unsolved. In addition, to facilitate cross-species comparisons and assignment of glycosyltransferases, we illustrated the biosynthetic pathways of the known CPS in a standardized format. Studying the intricate steps of pneumococcal CPS assembly promises to provide novel insights for drug and vaccine development as well as improve our understanding of related pathways in other species.
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Affiliation(s)
- Tong Su
- Infectious Diseases Translational Research Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, 117545, Singapore
| | - Rei Nakamoto
- Infectious Diseases Translational Research Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, 117545, Singapore
| | - Ye Yu Chun
- Infectious Diseases Translational Research Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, 117545, Singapore
| | - Wan Zhen Chua
- Infectious Diseases Translational Research Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, 117545, Singapore
| | - Jia Hui Chen
- Infectious Diseases Translational Research Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, 117545, Singapore
| | - Justin J Zik
- Infectious Diseases Translational Research Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, 117545, Singapore
| | - Lok-To Sham
- Infectious Diseases Translational Research Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, 117545, Singapore
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47
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Zheng L, Luo M, Kuang G, Liu Y, Liang D, Huang H, Yi X, Wang C, Wang Y, Xie Q, Zhi F. Capsular Polysaccharide From Bacteroides fragilis Protects Against Ulcerative Colitis in an Undegraded Form. Front Pharmacol 2020; 11:570476. [PMID: 33364945 PMCID: PMC7751226 DOI: 10.3389/fphar.2020.570476] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Accepted: 10/15/2020] [Indexed: 12/26/2022] Open
Abstract
The prominent human symbiont Bacteroides fragilis protects animals from intestinal diseases, such as ulcerative colitis, and its capsular polysaccharide plays a key role in reducing inflammation. B. fragilis strain ZY-312 was isolated from the feces of a healthy breast-fed infant, and the zwitterionic capsular polysaccharide zwitterionic polysaccharide, TP2, was extracted. In rats with 2,4-dinitrobenzenesulfonic acid (DNBS)-induced enteritis, TP2 at an optimal dose of 2.5 mg/kg could significantly alleviate enteritis and reduced the degree of intestinal adhesions, the intestinal ulcer area, and the incidence of ulcers in rats. To understand the underlying mechanism, TP2 was labeled with Fluorescein isothiocyanate and orally administered at a dose of 2.5 mg/kg in rats. TP2 was mainly distributed in the cecum and colorectum, but it was not detected in the blood and other organs except that a compound with a molecular weight greater than that of TP2-FITC was found in liver tissue. During the absorption, distribution, metabolism, and excretion, TP2 was indigestible. These results were further confirmed by investigation in the simulated gastric, intestinal fluid, and colonic fluid with fecal microbiota in vitro, where TP2 remained unaltered at different time points. Furthermore, flora composition was analyzed in simulated colonic fluid with TP2 added and it was found that TP2 increased the abundance of Faecalibacterium, Enterococcus romboutsia, and Ruminococcaceae, whereas the abundance of the phylum Proteobacteria represented by Sutterella, Desulfovibrio, and Enterobacteriaceae was decreased. However, the amount of short-chain fatty acids in the simulated colonic fluid was not changed by intestinal flora post-TP2 addition. In conclusion, these findings confirmed that TP2, a capsular polysaccharide of B. fragilis, protects against ulcerative colitis in an undegraded form.
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Affiliation(s)
- Lijun Zheng
- College of Life Science and Technology, Jinan University, Guangzhou, China.,Guangzhou ZhiYi Biotechnology Co. Ltd., Guangzhou, China
| | - Meihua Luo
- College of Life Science and Technology, Jinan University, Guangzhou, China
| | - Gaobo Kuang
- Guangzhou ZhiYi Biotechnology Co. Ltd., Guangzhou, China
| | - Yangyang Liu
- Guangzhou ZhiYi Biotechnology Co. Ltd., Guangzhou, China
| | - Debao Liang
- Guangzhou ZhiYi Biotechnology Co. Ltd., Guangzhou, China
| | - Haiqing Huang
- Guangzhou ZhiYi Biotechnology Co. Ltd., Guangzhou, China
| | - Xiaomin Yi
- Guangzhou ZhiYi Biotechnology Co. Ltd., Guangzhou, China
| | - Congfeng Wang
- Guangzhou ZhiYi Biotechnology Co. Ltd., Guangzhou, China
| | - Ye Wang
- Guangzhou ZhiYi Biotechnology Co. Ltd., Guangzhou, China
| | - Qiuling Xie
- College of Life Science and Technology, Jinan University, Guangzhou, China
| | - Fachao Zhi
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
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Unravelling the antimicrobial action of antidepressants on gut commensal microbes. Sci Rep 2020; 10:17878. [PMID: 33087796 PMCID: PMC7578019 DOI: 10.1038/s41598-020-74934-9] [Citation(s) in RCA: 88] [Impact Index Per Article: 17.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Accepted: 09/21/2020] [Indexed: 12/31/2022] Open
Abstract
Over the past decade, there has been increasing evidence highlighting the implication of the gut microbiota in a variety of brain disorders such as depression, anxiety, and schizophrenia. Studies have shown that depression affects the stability of gut microbiota, but the impact of antidepressant treatments on microbiota structure and metabolism remains underexplored. In this study, we investigated the in vitro antimicrobial activity of antidepressants from different therapeutic classes against representative strains of human gut microbiota. Six different antidepressants: phenelzine, venlafaxine, desipramine, bupropion, aripiprazole and (S)-citalopram have been tested for their antimicrobial activity against 12 commensal bacterial strains using agar well diffusion, microbroth dilution method, and colony counting. The data revealed an important antimicrobial activity (bacteriostatic or bactericidal) of different antidepressants against the tested strains, with desipramine and aripiprazole being the most inhibitory. Strains affiliating to most dominant phyla of human microbiota such as Akkermansia muciniphila, Bifidobacterium animalis and Bacteroides fragilis were significantly altered, with minimum inhibitory concentrations (MICs) ranged from 75 to 800 μg/mL. A significant reduction in bacterial viability was observed, reaching 5 logs cycle reductions with tested MICs ranged from 400 to 600 μg/mL. Our findings demonstrate that gut microbiota could be altered in response to antidepressant drugs.
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Chiu TW, Peng CJ, Chen MC, Hsu MH, Liang YH, Chiu CH, Fang JM, Lee YC. Constructing conjugate vaccine against Salmonella Typhimurium using lipid-A free lipopolysaccharide. J Biomed Sci 2020; 27:89. [PMID: 32831077 PMCID: PMC7443816 DOI: 10.1186/s12929-020-00681-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Accepted: 08/11/2020] [Indexed: 11/10/2022] Open
Abstract
Background Salmonella enterica serotype Typhimurium is a nontyphoidal and common foodborne pathogen that causes serious threat to humans. There is no licensed vaccine to prevent the nontyphoid bacterial infection caused by S. Typhimurium. Methods To develop conjugate vaccines, the bacterial lipid-A free lipopolysaccharide (LFPS) is prepared as the immunogen and used to synthesize the LFPS–linker–protein conjugates 6a–9b. The designed bifunctional linkers 1–5 comprising either an o-phenylenediamine or amine moiety are specifically attached to the exposed 3-deoxy-D-manno-octulosonic acid (Kdo), an α-ketoacid saccharide of LFPS, via condensation reaction or decarboxylative amidation. In addition to bovine serum albumin and ovalbumin, the S. Typhimurium flagellin (FliC) is also used as a self-adjuvanting protein carrier. Results The synthesized conjugate vaccines are characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and fast performance liquid chromatography (FPLC), and their contents of polysaccharides and protein are determined by phenol–sulfuric acid assay and bicinchoninic acid assay, respectively. Enzyme-linked immunosorbent assay (ELISA) shows that immunization of mouse with the LFPS–linker–protein vaccines at a dosage of 2.5 μg is sufficient to elicit serum immunoglobulin G (IgG) specific to S. Typhimurium lipopolysaccharide (LPS). The straight-chain amide linkers in conjugates 7a–9b do not interfere with the desired immune response. Vaccines 7a and 7b derived from either unfractionated LFPS or the high-mass portion show equal efficacy in induction of IgG antibodies. The challenge experiments are performed by oral gavage of S. Typhimurium pathogen, and vaccine 7c having FliC as the self-adjuvanting protein carrier exhibits a high vaccine efficacy of 74% with 80% mice survival rate at day 28 post the pathogen challenge. Conclusions This study demonstrates that lipid-A free lipopolysaccharide prepared from Gram-negative bacteria is an appropriate immunogen, in which the exposed Kdo is connected to bifunctional linkers to form conjugate vaccines. The decarboxylative amidation of Kdo is a novel and useful method to construct a relatively robust and low immunogenic straight-chain amide linkage. The vaccine efficacy is enhanced by using bacterial flagellin as the self-adjuvanting carrier protein. Graphical abstract ![]()
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Affiliation(s)
- Tzu-Wei Chiu
- Department of Chemistry, National Taiwan University, 1, Sec. 4, Roosevelt Rd, Taipei, 10617, Taiwan
| | - Chi-Jiun Peng
- Department of Chemistry, National Taiwan University, 1, Sec. 4, Roosevelt Rd, Taipei, 10617, Taiwan
| | - Ming-Cheng Chen
- Department of Chemistry, National Taiwan University, 1, Sec. 4, Roosevelt Rd, Taipei, 10617, Taiwan
| | - Mei-Hua Hsu
- Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, 5, Fuxing St., Guishan Dist, Taoyuan, 33302, Taiwan
| | - Yi-Hua Liang
- Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, 5, Fuxing St., Guishan Dist, Taoyuan, 33302, Taiwan
| | - Cheng-Hsun Chiu
- Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, 5, Fuxing St., Guishan Dist, Taoyuan, 33302, Taiwan. .,Department of Pediatrics, Chang Gung Children's Hospital, 5, Fuxing St., Guishan Dist, Taoyuan, 33302, Taiwan. .,Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, 259 Wenhua 1st Road, Guishan Dist, Taoyuan, 33302, Taiwan.
| | - Jim-Min Fang
- Department of Chemistry, National Taiwan University, 1, Sec. 4, Roosevelt Rd, Taipei, 10617, Taiwan. .,The Genomics Research Center, Academia Sinica, 128, Sec. 2, Academia Rd, Taipei, 11529, Taiwan.
| | - Yuan Chuan Lee
- Department of Biology, Johns Hopkins University, 3400 North Charles St, Baltimore, MD, 21218-2685, USA
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Gioia C, Lucchino B, Tarsitano MG, Iannuccelli C, Di Franco M. Dietary Habits and Nutrition in Rheumatoid Arthritis: Can Diet Influence Disease Development and Clinical Manifestations? Nutrients 2020; 12:nu12051456. [PMID: 32443535 PMCID: PMC7284442 DOI: 10.3390/nu12051456] [Citation(s) in RCA: 137] [Impact Index Per Article: 27.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Revised: 05/14/2020] [Accepted: 05/14/2020] [Indexed: 12/14/2022] Open
Abstract
Rheumatoid arthritis (RA) is a systemic, autoimmune disease characterized by joint involvement, with progressive cartilage and bone destruction. Genetic and environmental factors determine RA susceptibility. In recent years, an increasing number of studies suggested that diet has a central role in disease risk and progression. Several nutrients, such as polyunsaturated fatty acids, present anti-inflammatory and antioxidant properties, featuring a protective role for RA development, while others such as red meat and salt have a harmful effect. Gut microbiota alteration and body composition modifications are indirect mechanisms of how diet influences RA onset and progression. Possible protective effects of some dietary patterns and supplements, such as the Mediterranean Diet (MD), vitamin D and probiotics, could be a possible future adjunctive therapy to standard RA treatment. Therefore, a healthy lifestyle and nutrition have to be encouraged in patients with RA.
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Affiliation(s)
- Chiara Gioia
- Dipartimento di Scienze Cliniche, Internistiche, Anestesiologiche e Cardiovascolari-Reumatologia, Sapienza University of Rome, 00161 Roma, Italy; (C.G.); (C.I.); (M.D.F.)
| | - Bruno Lucchino
- Dipartimento di Scienze Cliniche, Internistiche, Anestesiologiche e Cardiovascolari-Reumatologia, Sapienza University of Rome, 00161 Roma, Italy; (C.G.); (C.I.); (M.D.F.)
- Correspondence: ; Tel.: +39-06-4997-4635
| | | | - Cristina Iannuccelli
- Dipartimento di Scienze Cliniche, Internistiche, Anestesiologiche e Cardiovascolari-Reumatologia, Sapienza University of Rome, 00161 Roma, Italy; (C.G.); (C.I.); (M.D.F.)
| | - Manuela Di Franco
- Dipartimento di Scienze Cliniche, Internistiche, Anestesiologiche e Cardiovascolari-Reumatologia, Sapienza University of Rome, 00161 Roma, Italy; (C.G.); (C.I.); (M.D.F.)
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