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Chen X, Shen M, Feng Q, Yang G, Tian R, Yao S, Zha H. Epidemiological characteristics, antifungal susceptibility, and mortality factors of candidemia in adults at a tertiary teaching hospital in Zunyi, China (2016-2023). BMC Infect Dis 2025; 25:726. [PMID: 40399823 PMCID: PMC12093603 DOI: 10.1186/s12879-025-11021-2] [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: 02/11/2025] [Accepted: 04/21/2025] [Indexed: 05/23/2025] Open
Abstract
BACKGROUND Candidemia, a common nosocomial bloodstream infection caused by Candida species, is associated with a high mortality rate. This study aimed to analyze the epidemiological characteristics, distribution of Candida species, antifungal susceptibility, and mortality risk factors of adult patients with candidemia in Zunyi, China. These findings are expected to inform treatment and prevention strategies for candidemia in this region. METHODS Clinical data, Candida species, antifungal susceptibility profiles, and prognosis of 92 patients with candidemia at the First People's Hospital of Zunyi (the Third Affiliated Hospital of Zunyi Medical University) from January 2016 to December 2023 were retrospectively analyzed. Univariate and multivariate logistic regression analyses were performed to analyze risk factors for patient death. RESULTS Analysis of 92 candidemia cases revealed an average incidence of 0.19% and mortality rate of 35.87%. Candida albicans was responsible for 33.70% of the infections, whereas non-C. albicans accounted for 66.30% of the total. Non-C. albicans was dominated by C. parapsilosis (31.52%), Nakaseomyces glabratus (18.48%), and C. tropicalis (13.04%). The susceptibility of all Candida species to amphotericin B exceeded 96%. C. albicans and C. parapsilosis showed greater than 70% susceptibility to fluconazole, itraconazole, and voriconazole, whereas C. tropicalis showed less than 60% susceptibility to these antifungal agents. Among the 33 dead patients, C. albicans was associated with a higher mortality rate than non-C. albicans (P = 0.007). Logistic multiple regression analysis showed that cardiovascular disease (OR = 8.913, 95% CI: 1.463-54.289, P = 0.018), kidney disease (OR = 13.672, 95% CI: 2.025-92.326, P = 0.007), and antifungal drug treatment duration less than 7 days (OR = 10.694, 95% CI: 1.841-62.112, P = 0.008) were independent risk factors for mortality in adult patients with candidemia. CONCLUSIONS The mortality rate among patients with candidemia remains high with C. albicans is the predominant pathogen in Zunyi, China. Cardiovascular disease, kidney disease, and antifungal drug treatment duration less than 7 days were independent risk factors for mortality in adult patients with candidemia. Therefore, greater attention should be paid to adult patients with risk factors for mortality to improve the outcomes of adult candidemia.
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Affiliation(s)
- Xianghao Chen
- Department of Laboratory Medicine, the First People's Hospital of Zunyi (the Third Affiliated Hospital of Zunyi Medical University), Zunyi, People's Republic of China
| | - Meijing Shen
- Department of Laboratory Medicine, the First People's Hospital of Zunyi (the Third Affiliated Hospital of Zunyi Medical University), Zunyi, People's Republic of China
| | - Qun Feng
- Department of Laboratory Medicine, the First People's Hospital of Zunyi (the Third Affiliated Hospital of Zunyi Medical University), Zunyi, People's Republic of China
| | - Guangwu Yang
- Department of Laboratory Medicine, the First People's Hospital of Zunyi (the Third Affiliated Hospital of Zunyi Medical University), Zunyi, People's Republic of China
| | - Rengui Tian
- Department of Laboratory Medicine, the First People's Hospital of Zunyi (the Third Affiliated Hospital of Zunyi Medical University), Zunyi, People's Republic of China
| | - Shifei Yao
- Department of Laboratory Medicine, the First People's Hospital of Zunyi (the Third Affiliated Hospital of Zunyi Medical University), Zunyi, People's Republic of China
| | - He Zha
- Department of Laboratory Medicine, the First People's Hospital of Zunyi (the Third Affiliated Hospital of Zunyi Medical University), Zunyi, People's Republic of China.
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2
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Guglietta S, Li X, Saxena D. Role of Fungi in Tumorigenesis: Promises and Challenges. ANNUAL REVIEW OF PATHOLOGY 2025; 20:459-482. [PMID: 39854185 DOI: 10.1146/annurev-pathmechdis-111523-023524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/26/2025]
Abstract
The mycobiome plays a key role in the host immune responses in homeostasis and inflammation. Recent studies suggest that an imbalance in the gut's fungi contributes to chronic, noninfectious diseases such as obesity, metabolic disorders, and cancers. Pathogenic fungi can colonize specific organs, and the gut mycobiome has been linked to the development and progression of various cancers, including colorectal, breast, head and neck, and pancreatic cancers. Some fungal species can promote tumorigenesis by triggering the complement system. However, in immunocompromised patients, fungi can also inhibit this activation and establish life-threatening infections. Interestingly, the interaction of the fungi and bacteria can also induce unique host immune responses. Recent breakthroughs and advancements in high-throughput sequencing of the gut and tumor mycobiomes are highlighting novel diagnostic and therapeutic opportunities for cancer. We discuss the latest developments in the field of cancer and the mycobiome and the potential benefits and challenges of antifungal therapies.
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Affiliation(s)
- Silvia Guglietta
- Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, South Carolina, USA
- Hollings Cancer Center, Charleston, South Carolina, USA
| | - Xin Li
- Department of Molecular Pathobiology, NYU College of Dentistry, New York, NY, USA;
- Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY, USA
- Department of Urology, NYU Grossman School of Medicine, New York, NY, USA
| | - Deepak Saxena
- Department of Molecular Pathobiology, NYU College of Dentistry, New York, NY, USA;
- Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY, USA
- Department of Surgery, NYU Grossman School of Medicine, New York, NY, USA
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3
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Lakhani DA, Deng F, Lin DDM. Infectious Diseases of the Brain and Spine: Fungal Diseases. Magn Reson Imaging Clin N Am 2024; 32:335-346. [PMID: 38555144 DOI: 10.1016/j.mric.2024.02.001] [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] [Indexed: 04/02/2024]
Abstract
Advances in treatments of autoimmune diseases, acquired immunodeficiency syndrome, organ transplantation, and the use of long-term devices have increased the rates of atypical infections due to prolonged immune suppression. There is a significant overlap in imaging findings of various fungal infections affecting the central nervous system (CNS), often mimicking those seen in neoplastic and noninfectious inflammatory conditions. Nonetheless, there are imaging characteristics that can aid in distinguishing certain atypical infections. Hence, familiarity with a wide range of infectious agents is an important part of diagnostic neuroradiology. In this article, an in-depth review of fungal diseases of the CNS is provided.
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Affiliation(s)
- Dhairya A Lakhani
- Division of Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Phipps B-100 Baltimore, MD 21287, USA
| | - Francis Deng
- Division of Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Phipps B-100 Baltimore, MD 21287, USA
| | - Doris D M Lin
- Division of Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Phipps B-100 Baltimore, MD 21287, USA.
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4
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Sadiq KO, Desai S, Miller S, Abualnadi YD, Khalil ZM, Khan Z, Amjadi N, Ravindra VM, Tekle W, Georgiadis AL, Hassan AE. Epidural anesthesia causes outbreak of mycotic aneurysms: complications of Fusarium solani meningitis. J Neurointerv Surg 2024:jnis-2023-021300. [PMID: 38418228 DOI: 10.1136/jnis-2023-021300] [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: 11/24/2023] [Accepted: 02/05/2024] [Indexed: 03/01/2024]
Abstract
BACKGROUND A health advisory was issued in response to a fungal meningitis outbreak linked to epidural anesthesia exposure in two plastic surgery clinics in Mexico, from January 1 to May 13, 2023. This descriptive analysis describes the neuroendovascular and neurosurgical observations and management of patients treated at a single stroke center located along the US-Mexico Border. METHODS We conducted a retrospective chart review of fungal meningitis patients presenting between April and July 2023. RESULTS Among the patients diagnosed with fungal meningitis (n=12), the majority (n=11) were afflicted with angio-invasive Fusarium solani. 83% received dual antifungal therapy, with 40% initiated on alternate-day intrathecal amphotericin B. Diagnostic cerebral angiography was performed on all patients, revealing aneurysms in 58% of cases, predominantly within the posterior circulation, notably the basilar artery, with a median size of 4.2 mm (IQR 3.3-4.8). Treatment strategies included flow diversion (70%) and primary coiling (14%) for aneurysms. Ventriculostomy placement was undertaken in 67% of patients, with 37.5% of these requiring conversion to ventriculoperitoneal shunts. Subarachnoid hemorrhage development was uniformly associated with 100% mortality. CONCLUSIONS In patients presenting with Fusarium solani meningitis, weekly angiographic surveillance proved instrumental for monitoring aneurysm and vasospasm development. Conventional angiography outperformed CT angiography due to its enhanced ability to detect small aneurysms. A proactive approach to aneurysm treatment is advocated, given their elevated rupture risk. While our findings suggest the potential reversibility of angiographic vasospasm with effective antifungal treatment, we acknowledge the challenge of drawing definitive conclusions based on a limited sample size.
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Affiliation(s)
- Kaiser O'Sahil Sadiq
- Department of Neuroscience, Valley Baptist Medical Center - Harlingen, Harlingen, Texas, USA
| | - Sohum Desai
- Department of Neuroscience, Valley Baptist Medical Center - Harlingen, Harlingen, Texas, USA
- Surgery, The University of Texas Rio Grande Valley School of Medicine, Edinburg, Texas, USA
| | - Samantha Miller
- Department of Neuroscience, Valley Baptist Medical Center - Harlingen, Harlingen, Texas, USA
| | - Yazan D Abualnadi
- Department of Neuroscience, Valley Baptist Medical Center - Harlingen, Harlingen, Texas, USA
| | - Zorain Mustafa Khalil
- Department of Neuroscience, Valley Baptist Medical Center - Harlingen, Harlingen, Texas, USA
| | - Zooha Khan
- Department of Neuroscience, Valley Baptist Medical Center - Harlingen, Harlingen, Texas, USA
| | - Nazaneen Amjadi
- Department of Neuroscience, Valley Baptist Medical Center - Harlingen, Harlingen, Texas, USA
| | - Vijay M Ravindra
- Department of Neurosurgery, University of Utah Health Clinical Neurosciences Center, Salt Lake City, Utah, USA
| | | | - Alexandros L Georgiadis
- Department of Neuroscience, Valley Baptist Medical Center - Harlingen, Harlingen, Texas, USA
| | - Ameer E Hassan
- Department of Neurology, University of Texas Rio Grande Valley, Harlingen, Texas, USA
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5
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Shintaku M. Esophageal intramural pseudodiverticulosis. World J Gastroenterol 2024; 30:137-145. [PMID: 38312118 PMCID: PMC10835521 DOI: 10.3748/wjg.v30.i2.137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2023] [Revised: 12/21/2023] [Accepted: 12/28/2023] [Indexed: 01/12/2024] Open
Abstract
Esophageal intramural pseudodiverticulosis (EIPD) is a disease of unknown pathogenesis characterized by usually systemic, cystic dilatation of the excretory ducts of esophageal submucosal glands. In this article, I review the epidemiology, clinical manifestations, endoscopic findings, esophagographic findings, and histopathology of EIPD. I also discuss the etiology and possible pathogenesis of EIPD based on my experiences with this disease and a review of the literature. EIPD usually presents with dysphagia in middle-aged individuals. It is often complicated with secondary infections, most commonly candidiasis. On esophagography, EIPD is delineated as small, multiple, flask-shaped outward projections within the esophageal wall. In recent years, EIPD has been mainly diagnosed by endoscopic findings of multiple, localized, small mucosal depressions. The orifices of the "pseudodiverticula" periodically open and close, and excrete mucus onto the mucosal surface. On histopathological examination, the luminal surface of dilated ducts in EIPD is covered by multilayered, hyperplastic epithelial cells, but myoepithelial cells in the glandular acini are well preserved. Treatment of EIPD is usually symptomatic therapy, and prevention of the infectious complications is important. The etiology and pathogenesis of EIPD are largely unknown, but functional abnormalities of autonomic nerve fibers innervating the esophageal glands likely play an important role, since the structures of the glands are basically preserved in this disease.
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Affiliation(s)
- Masako Shintaku
- Department of Gastroenterology, Japan Community Healthcare Organization Hoshigaoka Medical Center, Hirakata 573-8511, Osaka, Japan
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6
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Lawal SA, Voisin A, Olof H, Bording-Jorgensen M, Armstrong H. Diversity of the microbiota communities found in the various regions of the intestinal tract in healthy individuals and inflammatory bowel diseases. Front Immunol 2023; 14:1242242. [PMID: 38022505 PMCID: PMC10654633 DOI: 10.3389/fimmu.2023.1242242] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Accepted: 10/20/2023] [Indexed: 12/01/2023] Open
Abstract
The severe and chronic inflammatory bowel diseases (IBD), Crohn disease and ulcerative colitis, are characterized by persistent inflammation and gut damage. There is an increasing recognition that the gut microbiota plays a pivotal role in IBD development and progression. However, studies of the complete microbiota composition (bacteria, fungi, viruses) from precise locations within the gut remain limited. In particular, studies have focused primarily on the bacteriome, with available methods limiting evaluation of the mycobiome (fungi) and virome (virus). Furthermore, while the different segments of the small and large intestine display different functions (e.g., digestion, absorption, fermentation) and varying microenvironment features (e.g., pH, metabolites), little is known about the biogeography of the microbiota in different segments of the intestinal tract or how this differs in IBD. Here, we highlight evidence of the differing microbiota communities of the intestinal sub-organs in healthy and IBD, along with method summaries to improve future studies.
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Affiliation(s)
- Samuel Adefisoye Lawal
- Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada
- Manitoba Centre for Proteomics and Systems Biology, University of Manitoba, Winnipeg, MB, Canada
- IBD Clinical and Research Centre, University of Manitoba, Winnipeg, MB, Canada
| | - Athalia Voisin
- Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada
- Manitoba Centre for Proteomics and Systems Biology, University of Manitoba, Winnipeg, MB, Canada
- IBD Clinical and Research Centre, University of Manitoba, Winnipeg, MB, Canada
| | - Hana Olof
- Manitoba Centre for Proteomics and Systems Biology, University of Manitoba, Winnipeg, MB, Canada
- IBD Clinical and Research Centre, University of Manitoba, Winnipeg, MB, Canada
- Department of Immunology, University of Manitoba, Winnipeg, MB, Canada
| | | | - Heather Armstrong
- Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada
- Manitoba Centre for Proteomics and Systems Biology, University of Manitoba, Winnipeg, MB, Canada
- IBD Clinical and Research Centre, University of Manitoba, Winnipeg, MB, Canada
- Department of Immunology, University of Manitoba, Winnipeg, MB, Canada
- Department of Pediatrics, University of Alberta, Edmonton, AB, Canada
- Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada
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7
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Kunimitsu A, Ujiie N, Sato C, Taniyama Y, Okamoto H, Fukutomi T, Ozawa Y, Ohnuma S, Unno M, Kamei T. Esophageal Intramural Pseudodiverticulosis Diagnosed by Combining Esophagogastroduodenoscopy, Esophagography, and High-resolution Manometry. Intern Med 2023; 62:1495-1499. [PMID: 36223924 PMCID: PMC10258114 DOI: 10.2169/internalmedicine.0337-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Accepted: 09/04/2022] [Indexed: 04/07/2023] Open
Abstract
Esophageal intramural pseudodiverticulosis (EIPD) is a rare disease. A 78-year-old man with dysphagia presented to our hospital. The presence of diffuse esophageal spasm was suspected by his primary-care doctor. High-resolution manometry (HRM) showed no abnormal findings. The patient was diagnosed with EIPD and Candida esophagitis, by esophagogastroduodenoscopy (EGD) and esophagography. His symptoms improved after symptomatic treatment for Candida esophagitis with oral administration of an antifungal drug. EIPD should be considered in patients with dysphagia; EGD and esophagography should be performed when diagnosing EIPD.
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Affiliation(s)
- Atsushi Kunimitsu
- Department of Surgery, Tohoku University Graduate School of Medicine, Japan
| | - Naoto Ujiie
- Department of Surgery, Tohoku University Graduate School of Medicine, Japan
| | - Chiaki Sato
- Department of Surgery, Tohoku University Graduate School of Medicine, Japan
| | - Yusuke Taniyama
- Department of Surgery, Tohoku University Graduate School of Medicine, Japan
| | - Hiroshi Okamoto
- Department of Surgery, Tohoku University Graduate School of Medicine, Japan
| | - Toshiaki Fukutomi
- Department of Surgery, Tohoku University Graduate School of Medicine, Japan
| | - Yohei Ozawa
- Department of Surgery, Tohoku University Graduate School of Medicine, Japan
| | - Shinobu Ohnuma
- Department of Surgery, Tohoku University Graduate School of Medicine, Japan
| | - Michiaki Unno
- Department of Surgery, Tohoku University Graduate School of Medicine, Japan
| | - Takashi Kamei
- Department of Surgery, Tohoku University Graduate School of Medicine, Japan
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8
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Rozaliyani A, Antariksa B, Nurwidya F, Zaini J, Setianingrum F, Hasan F, Nugrahapraja H, Yusva H, Wibowo H, Bowolaksono A, Kosmidis C. The Fungal and Bacterial Interface in the Respiratory Mycobiome with a Focus on Aspergillus spp. Life (Basel) 2023; 13:life13041017. [PMID: 37109545 PMCID: PMC10142979 DOI: 10.3390/life13041017] [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: 02/27/2023] [Revised: 04/08/2023] [Accepted: 04/12/2023] [Indexed: 04/29/2023] Open
Abstract
The heterogeneity of the lung microbiome and its alteration are prevalently seen among chronic lung diseases patients. However, studies to date have primarily focused on the bacterial microbiome in the lung rather than fungal composition, which might play an essential role in the mechanisms of several chronic lung diseases. It is now well established that Aspergillus spp. colonies may induce various unfavorable inflammatory responses. Furthermore, bacterial microbiomes such as Pseudomonas aeruginosa provide several mechanisms that inhibit or stimulate Aspergillus spp. life cycles. In this review, we highlighted fungal and bacterial microbiome interactions in the respiratory tract, with a focus on Aspergillus spp.
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Affiliation(s)
- Anna Rozaliyani
- Department of Parasitology, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia
- Indonesia Pulmonary Mycoses Centre, Jakarta 10430, Indonesia
| | - Budhi Antariksa
- Department of Pulmonoloy and Respiratory Medicine, Faculty of Medicinie, Universitas Indonesia, Persahabatan National Respiratory Referral Hospital, Jakarta 13230, Indonesia
| | - Fariz Nurwidya
- Department of Pulmonoloy and Respiratory Medicine, Faculty of Medicinie, Universitas Indonesia, Persahabatan National Respiratory Referral Hospital, Jakarta 13230, Indonesia
| | - Jamal Zaini
- Department of Pulmonoloy and Respiratory Medicine, Faculty of Medicinie, Universitas Indonesia, Persahabatan National Respiratory Referral Hospital, Jakarta 13230, Indonesia
| | - Findra Setianingrum
- Department of Parasitology, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia
- Indonesia Pulmonary Mycoses Centre, Jakarta 10430, Indonesia
| | - Firman Hasan
- Indonesia Pulmonary Mycoses Centre, Jakarta 10430, Indonesia
| | - Husna Nugrahapraja
- Life Science and Biotechnology, Bandung Institute of Technology, Bandung 40312, Indonesia
| | - Humaira Yusva
- Magister Program of Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia
| | - Heri Wibowo
- Department of Parasitology, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia
| | - Anom Bowolaksono
- Department of Biology, Faculty of Mathematics and Natural Sciences (FMIPA), Universitas Indonesia, Depok 16424, Indonesia
| | - Chris Kosmidis
- Manchester Academic Health Science Centre, Division of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M23 9LT, UK
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9
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Li XV, Leonardi I, Putzel GG, Semon A, Fiers WD, Kusakabe T, Lin WY, Gao IH, Doron I, Gutierrez-Guerrero A, DeCelie MB, Carriche GM, Mesko M, Yang C, Naglik JR, Hube B, Scherl EJ, Iliev ID. Immune regulation by fungal strain diversity in inflammatory bowel disease. Nature 2022; 603:672-678. [PMID: 35296857 PMCID: PMC9166917 DOI: 10.1038/s41586-022-04502-w] [Citation(s) in RCA: 176] [Impact Index Per Article: 58.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Accepted: 02/02/2022] [Indexed: 12/21/2022]
Abstract
The fungal microbiota (mycobiota) is an integral part of the complex multikingdom microbial community colonizing the mammalian gastrointestinal tract and has an important role in immune regulation1-6. Although aberrant changes in the mycobiota have been linked to several diseases, including inflammatory bowel disease3-9, it is currently unknown whether fungal species captured by deep sequencing represent living organisms and whether specific fungi have functional consequences for disease development in affected individuals. Here we developed a translational platform for the functional analysis of the mycobiome at the fungal-strain- and patient-specific level. Combining high-resolution mycobiota sequencing, fungal culturomics and genomics, a CRISPR-Cas9-based fungal strain editing system, in vitro functional immunoreactivity assays and in vivo models, this platform enables the examination of host-fungal crosstalk in the human gut. We discovered a rich genetic diversity of opportunistic Candida albicans strains that dominate the colonic mucosa of patients with inflammatory bowel disease. Among these human-gut-derived isolates, strains with high immune-cell-damaging capacity (HD strains) reflect the disease features of individual patients with ulcerative colitis and aggravated intestinal inflammation in vivo through IL-1β-dependent mechanisms. Niche-specific inflammatory immunity and interleukin-17A-producing T helper cell (TH17 cell) antifungal responses by HD strains in the gut were dependent on the C. albicans-secreted peptide toxin candidalysin during the transition from a benign commensal to a pathobiont state. These findings reveal the strain-specific nature of host-fungal interactions in the human gut and highlight new diagnostic and therapeutic targets for diseases of inflammatory origin.
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Affiliation(s)
- Xin V Li
- Gastroenterology and Hepatology Division, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA
- The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY, USA
| | - Irina Leonardi
- Gastroenterology and Hepatology Division, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA
- The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY, USA
| | - Gregory G Putzel
- The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY, USA
| | - Alexa Semon
- Gastroenterology and Hepatology Division, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA
- The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY, USA
| | - William D Fiers
- Gastroenterology and Hepatology Division, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA
- The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY, USA
| | - Takato Kusakabe
- Gastroenterology and Hepatology Division, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA
- The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY, USA
| | - Woan-Yu Lin
- Gastroenterology and Hepatology Division, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA
- The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY, USA
- Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, Cornell University, New York, NY, USA
| | - Iris H Gao
- Gastroenterology and Hepatology Division, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA
- The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY, USA
- Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, Cornell University, New York, NY, USA
| | - Itai Doron
- Gastroenterology and Hepatology Division, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA
- The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY, USA
| | - Alejandra Gutierrez-Guerrero
- Gastroenterology and Hepatology Division, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA
- The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY, USA
| | - Meghan B DeCelie
- The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY, USA
| | - Guilhermina M Carriche
- Gastroenterology and Hepatology Division, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA
- The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY, USA
| | - Marissa Mesko
- The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY, USA
| | - Chen Yang
- Department of Pathology, Yale School of Medicine, Yale University, New Haven, CT, USA
| | - Julian R Naglik
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, UK
| | - Bernhard Hube
- Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Jena, Germany
- Institute of Microbiology, FriedrichSchiller University, Jena, Germany
| | - Ellen J Scherl
- Gastroenterology and Hepatology Division, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA
- The Jill Roberts Center for Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY, USA
| | - Iliyan D Iliev
- Gastroenterology and Hepatology Division, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA.
- The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY, USA.
- Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, Cornell University, New York, NY, USA.
- Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY, USA.
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Romo JA, Kumamoto CA. Characterization of the Effects of Candida Gastrointestinal Colonization on Clostridioides difficile Infection in a Murine Model. Methods Mol Biol 2022; 2542:271-285. [PMID: 36008672 DOI: 10.1007/978-1-0716-2549-1_20] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
The role of fungal colonizers of the gastrointestinal tract during disease states is not well understood. Antibiotic treatment renders patients highly susceptible to infection by the bacterial pathogen C. difficile while also leading to blooms in fungal commensals, setting the stage for trans-kingdom interactions. Here, we describe a murine model of Candida gastrointestinal colonization coupled to a C. difficile infection (CDI) model, the measurement of CFU of both organisms, and collection of cecum and colon contents for the purpose of quantifying C. difficile toxin production. Additionally, we describe how to induce and purify C. difficile spores.
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Affiliation(s)
- Jesús A Romo
- Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USA
| | - Carol A Kumamoto
- Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USA.
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11
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Alterations of the gut mycobiome in patients with MS. EBioMedicine 2021; 71:103557. [PMID: 34455391 PMCID: PMC8399064 DOI: 10.1016/j.ebiom.2021.103557] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 07/21/2021] [Accepted: 08/13/2021] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND The mycobiome is the fungal component of the gut microbiome and is implicated in several autoimmune diseases. However, its role in MS has not been studied. METHODS In this case-control observational study, we performed ITS sequencing and characterised the gut mycobiome in people with MS (pwMS) and healthy controls at baseline and after six months. FINDINGS The mycobiome had significantly higher alpha diversity and inter-subject variation in pwMS than controls. Saccharomyces and Aspergillus were over-represented in pwMS. Saccharomyces was positively correlated with circulating basophils and negatively correlated with regulatory B cells, while Aspergillus was positively correlated with activated CD16+ dendritic cells in pwMS. Different mycobiome profiles, defined as mycotypes, were associated with different bacterial microbiome and immune cell subsets in the blood. Initial treatment with dimethyl fumarate, a common immunomodulatory therapy which also has fungicidal activity, did not cause uniform gut mycobiome changes across all pwMS. INTERPRETATION There is an alteration of the gut mycobiome in pwMS, compared to healthy controls. Further study is required to assess any causal association of the mycobiome with MS and its direct or indirect interactions with bacteria and autoimmunity. FUNDING This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS102633-04 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). Cantoni C. was supported by the National MS Society Career Transition Fellowship (TA-1805-31003) and by donations from Whitelaw Terry, Jr. / Valerie Terry Fund. Ghezzi L. was supported by the Italian Multiple Sclerosis Society research fellowship (FISM 2018/B/1) and the National Multiple Sclerosis Society Post-Doctoral Fellowship (FG- 1907-34474). Anne Cross was supported by The Manny & Rosalyn Rosenthal-Dr. John L. Trotter MS Center Chair in Neuroimmunology of the Barnes-Jewish Hospital Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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Vallianou N, Kounatidis D, Christodoulatos GS, Panagopoulos F, Karampela I, Dalamaga M. Mycobiome and Cancer: What Is the Evidence? Cancers (Basel) 2021; 13:cancers13133149. [PMID: 34202433 PMCID: PMC8269322 DOI: 10.3390/cancers13133149] [Citation(s) in RCA: 57] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2021] [Revised: 06/21/2021] [Accepted: 06/23/2021] [Indexed: 02/07/2023] Open
Abstract
Simple Summary Although comprising a much smaller proportion of the human microbiome, the fungal community has gained much more attention lately due to its multiple and yet undiscovered interactions with the human bacteriome and the host. Head and neck cancer carcinoma, colorectal carcinoma, and pancreatic ductal adenocarcinoma have been associated with dissimilarities in the composition of the mycobiome between cases with cancer and non-cancer subjects. In particular, an abundance of Malassezia has been associated with the onset and progression of colorectal carcinoma and pancreatic adenocarcinoma, while the genera Schizophyllum, a member of the oral mycobiome, is suggested to exhibit anti-cancer potential. The use of multi-omics will further assist in establishing whether alterations in the human mycobiome are causal or a consequence of specific types of cancers. Abstract Background: To date, most researchhas focused on the bacterial composition of the human microbiota. In this review, we synopsize recent data on the human mycobiome and cancer, highlighting specific cancer types based on current available evidence, presenting interesting perspectives and limitations of studies and laboratory methodologies. Recent findings: Head and neck cancer carcinoma (HNCC), colorectal carcinoma (CRC) and pancreatic ductal adenocarcinoma (PDA) have been associated with dissimilarities in the composition of mycobiota between cancer cases and non-cancer participants. Overall, fungal dysbiosis with decreased fungal richness and diversity was common in cancer patients; however, a specific mycobiotic signature in HNSCC or CRC has not emerged. Different strains of Candida albicans have been identified among cases with HNCC, whilst Lichtheimia corymbifera, a member of the Mucoraceae family, has been shown to predominate among patients with oral tongue cancer. Virulence factors of Candida spp. include the formation of biofilm and filamentation, and the secretion of toxins and metabolites. CRC patients present a dysregulated ratio of Basidiomycota/Ascomycota. Abundance of Malassezia has been linked to the occurrence and progression of CRC and PDA, particularly in animal models of PDA. Interestingly, Schizophyllum, a component of the oral mycobiome, may exhibit anti-cancer potential. Conclusion: The human mycobiome, per se, along with its interactions with the human bacteriome and the host, may be implicated in the promotion and progression of carcinogenesis. Fungi may be used as diagnostic and prognostic/predictive tools or treatment targets for cancer in the coming years. More large-scale, prospective, multicentric and longitudinal studies with an integrative multi-omics methodology are required to examine the precise contribution of the mycobiome in the etiopathogenesis of cancer, and to delineate whether changes that occur in the mycobiome are causal or consequent of cancer.
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Affiliation(s)
- Natalia Vallianou
- First Department of Internal Medicine, Evangelismos General Hospital, 45-47 Ipsilantou Str., 10676 Athens, Greece; (D.K.); (F.P.)
- Correspondence: (N.V.); (M.D.)
| | - Dimitris Kounatidis
- First Department of Internal Medicine, Evangelismos General Hospital, 45-47 Ipsilantou Str., 10676 Athens, Greece; (D.K.); (F.P.)
| | - Gerasimos Socrates Christodoulatos
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias, Goudi, 11527 Athens, Greece;
| | - Fotis Panagopoulos
- First Department of Internal Medicine, Evangelismos General Hospital, 45-47 Ipsilantou Str., 10676 Athens, Greece; (D.K.); (F.P.)
| | - Irene Karampela
- Second Department of Critical Care, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, 1 Rimini St, Haidari, 12462 Athens, Greece;
| | - Maria Dalamaga
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias, Goudi, 11527 Athens, Greece;
- Correspondence: (N.V.); (M.D.)
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Suárez-Jaramillo A, Baldeón ME, Prado B, Fornasini M, Cohen H, Flores N, Salvador I, Cargua O, Realpe J, Cárdenas PA. Duodenal microbiome in patients with or without Helicobacter pylori infection. Helicobacter 2020; 25:e12753. [PMID: 32896972 DOI: 10.1111/hel.12753] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2020] [Revised: 07/06/2020] [Accepted: 07/25/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Intestinal microbiota are recognized as an organ with important physiological functions whose alterations have been associated with common diseases including inflammatory intestinal conditions, malnutrition, type-2 diabetes, and cardiovascular diseases. The composition and function of the microbiota in the distal part of the intestine has been mainly described, while there is limited information on the small intestine microbiota. The objective of the present study was to describe the duodenal microbiome in individuals with dyspepsia in the presence or absence of Helicobacter pylori gastric infection. MATERIALS AND METHODS Thirty-eight biopsies from the proximal duodenum of uninfected and 37 from H pylori-infected individuals were analyzed. Microbiota composition was assessed by PCR amplification and sequencing of 16S rRNA and ITS genes; sequences were analyzed with QIIME2. RESULTS AND CONCLUSIONS At the phyla level, Proteobacteria, Bacteroidetes, Firmicutes, Actinobacteria, and Fusobacteria were predominant in the mucosal associated duodenal microbiota (MAM); at the genera level, we observed the predominance of Ralstonia, Streptococcus, Pseudomonas, Haemophilus, Herbaspirillum, Neisseria, and Veillonella. Microbiota α-diversity was higher in H pylori-infected individuals than in non-infected ones. In terms of β-diversity metrics, there was a statistically significant difference between groups. Also, relative abundance of Haemophilus, Neisseria, Prevotella pallens, Prevotella 7, and Streptococcus was greater in H pylori-infected patients. In infected patients, several types of H pylori were present in duodenal MAM. Finally, the majority of duodenal samples had fungi sequences; the most common taxa observed were Recurvomyces followed by Ascomycota and Basidiomycota.
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Affiliation(s)
| | - Manuel E Baldeón
- Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigación Biomédica, Universidad Tecnológica Equinoccial, Quito, Ecuador
| | - Belén Prado
- Instituto de Microbiología, COCIBA, Universidad San Francisco de Quito, Quito, Ecuador
| | - Marco Fornasini
- Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigación Biomédica, Universidad Tecnológica Equinoccial, Quito, Ecuador
| | - Henry Cohen
- Facultad de Medicina, Universidad de la República Uruguay, Montevideo, Uruguay
| | - Nancy Flores
- Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigación Biomédica, Universidad Tecnológica Equinoccial, Quito, Ecuador
| | - Iván Salvador
- Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigación Biomédica, Universidad Tecnológica Equinoccial, Quito, Ecuador
| | - Oswaldo Cargua
- Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigación Biomédica, Universidad Tecnológica Equinoccial, Quito, Ecuador
| | - José Realpe
- Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigación Biomédica, Universidad Tecnológica Equinoccial, Quito, Ecuador
| | - Paul A Cárdenas
- Instituto de Microbiología, COCIBA, Universidad San Francisco de Quito, Quito, Ecuador
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Markey L, Hooper A, Melon LC, Baglot S, Hill MN, Maguire J, Kumamoto CA. Colonization with the commensal fungus Candida albicans perturbs the gut-brain axis through dysregulation of endocannabinoid signaling. Psychoneuroendocrinology 2020; 121:104808. [PMID: 32739746 PMCID: PMC7572798 DOI: 10.1016/j.psyneuen.2020.104808] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2020] [Revised: 06/08/2020] [Accepted: 07/20/2020] [Indexed: 02/06/2023]
Abstract
Anxiety disorders are the most prevalent mental health disorder worldwide, with a lifetime prevalence of 5-7 % of the human population. Although the etiology of anxiety disorders is incompletely understood, one aspect of host health that affects anxiety disorders is the gut-brain axis. Adolescence is a key developmental window in which stress and anxiety disorders are a major health concern. We used adolescent female mice in a gastrointestinal (GI) colonization model to demonstrate that the commensal fungus Candida albicans affects host health via the gut-brain axis. In mice, bacterial members of the gut microbiota can influence the host gut-brain axis, affecting anxiety-like behavior and the hypothalamus-pituitary-adrenal (HPA) axis which produces the stress hormone corticosterone (CORT). Here we showed that mice colonized with C. albicans demonstrated increased anxiety-like behavior and increased basal production of CORT as well as dysregulation of CORT production following acute stress. The HPA axis and anxiety-like behavior are negatively regulated by the endocannabinoid N-arachidonoylethanolamide (AEA). We demonstrated that C. albicans-colonized mice exhibited changes in the endocannabinoidome. Further, increasing AEA levels using the well-characterized fatty acid amide hydrolase (FAAH) inhibitor URB597 was sufficient to reverse both neuroendocrine phenotypes in C. albicans-colonized mice. Thus, a commensal fungus that is a common colonizer of humans had widespread effects on the physiology of its host. To our knowledge, this is the first report of microbial manipulation of the endocannabinoid (eCB) system that resulted in neuroendocrine changes contributing to anxiety-like behavior.
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Affiliation(s)
- Laura Markey
- Department of Molecular Biology and Microbiology, Tufts University, 150 Harrison Ave, Boston, MA, 02111, United States
| | - Andrew Hooper
- Department of Neuroscience, Tufts University, 150 Harrison Ave, Boston, MA, 02111, United States
| | - Laverne C Melon
- Department of Neuroscience, Tufts University, 150 Harrison Ave, Boston, MA, 02111, United States
| | - Samantha Baglot
- Hotchkiss Brain Institute, University of Calgary, Calgary, AB, T2N1Z4, Canada
| | - Matthew N Hill
- Hotchkiss Brain Institute, University of Calgary, Calgary, AB, T2N1Z4, Canada
| | - Jamie Maguire
- Department of Neuroscience, Tufts University, 150 Harrison Ave, Boston, MA, 02111, United States
| | - Carol A Kumamoto
- Department of Molecular Biology and Microbiology, Tufts University, 150 Harrison Ave, Boston, MA, 02111, United States.
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The cultivable microbiota of the human distal ileum. Clin Microbiol Infect 2020; 27:912.e7-912.e13. [PMID: 32835795 DOI: 10.1016/j.cmi.2020.08.021] [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: 02/12/2020] [Revised: 08/14/2020] [Accepted: 08/15/2020] [Indexed: 12/17/2022]
Abstract
OBJECTIVES The existing literature on the microbiota of the ileum is inconsistent. To further characterize the microbiota, we analysed samples obtained directly from resected ileums used for urinary diversion after radical cystectomy. METHODS We included 150 patients with bladder cancer operated on from March 2016 to March 2019. Samples obtained by rubbing a swab against the ileal mucosa 25 cm from the ileocecal valve were cultivated at the local laboratory. Microbial colonies were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF). RESULTS The microbial density of the distal ileum was low. Among our samples, 79% (95% confidence interval (CI) 71%, 84%) harboured less than 1.6 × 104 cfu/mL, whereas 36% (95% CI 28%, 44%) harboured less than 1.6 × 103 cfu/mL. The flora was dominated by viridans streptococci, Candida, Actinomyces, Rothia and Lactobacillus species. Colon-related bacteria i.e. strict anaerobic bacteria, Enterobacteriales and enterococci, were recovered from 14% of the samples. Constipation was associated with increased recovery of colon-related bacteria. Antibiotic treatment prior to surgical procedures did not affect culture results. Increased age was significantly associated with more substantial fungal growth and use of proton pump inhibitors seemed to increase both bacterial and fungal growth. CONCLUSIONS The microbiota of the human distal ileum is sparse and differs significantly from the colonic microbiota both quantitatively and by composition. These findings contradict recent metagenomics studies based on samples collected by retrograde colonoscopy and emphasize the crucial importance of adequate sampling techniques.
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Three Related Enzymes in Candida albicans Achieve Arginine- and Agmatine-Dependent Metabolism That Is Essential for Growth and Fungal Virulence. mBio 2020; 11:mBio.01845-20. [PMID: 32788384 PMCID: PMC7439472 DOI: 10.1128/mbio.01845-20] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Amino acid metabolism is crucial for fungal growth and development. Ureohydrolases produce amines when acting on l-arginine, agmatine, and guanidinobutyrate (GB), and these enzymes generate ornithine (by arginase), putrescine (by agmatinase), or GABA (by 4-guanidinobutyrase or GBase). Candida albicans can metabolize and grow on arginine, agmatine, or guanidinobutyrate as the sole nitrogen source. Three related C. albicans genes whose sequences suggested that they were putative arginase or arginase-like genes were examined for their role in these metabolic pathways. Of these, Car1 encoded the only bona fide arginase, whereas we provide evidence that the other two open reading frames, orf19.5862 and orf19.3418, encode agmatinase and guanidinobutyrase (Gbase), respectively. Analysis of strains with single and multiple mutations suggested the presence of arginase-dependent and arginase-independent routes for polyamine production. CAR1 played a role in hyphal morphogenesis in response to arginine, and the virulence of a triple mutant was reduced in both Galleria mellonella and Mus musculus infection models. In the bloodstream, arginine is an essential amino acid that is required by phagocytes to synthesize nitric oxide (NO). However, none of the single or multiple mutants affected host NO production, suggesting that they did not influence the oxidative burst of phagocytes.IMPORTANCE We show that the C. albicans ureohydrolases arginase (Car1), agmatinase (Agt1), and guanidinobutyrase (Gbu1) can orchestrate an arginase-independent route for polyamine production and that this is important for C. albicans growth and survival in microenvironments of the mammalian host.
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Phosphate in Virulence of Candida albicans and Candida glabrata. J Fungi (Basel) 2020; 6:jof6020040. [PMID: 32224872 PMCID: PMC7344514 DOI: 10.3390/jof6020040] [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: 03/04/2020] [Revised: 03/21/2020] [Accepted: 03/22/2020] [Indexed: 12/22/2022] Open
Abstract
Candida species are the most commonly isolated invasive human fungal pathogens. A role for phosphate acquisition in their growth, resistance against host immune cells, and tolerance of important antifungal medications is becoming apparent. Phosphorus is an essential element in vital components of the cell, including chromosomes and ribosomes. Producing the energy currency of the cell, ATP, requires abundant inorganic phosphate. A comparison of the network of regulators and effectors that controls phosphate acquisition and intracellular distribution, the PHO regulon, between the model yeast Saccharomyces cerevisiae, a plant saprobe, its evolutionarily close relative C. glabrata, and the more distantly related C. albicans, highlights the need to coordinate phosphate homeostasis with adenylate biosynthesis for ATP production. It also suggests that fungi that cope with phosphate starvation as they invade host tissues, may link phosphate acquisition to stress responses as an efficient mechanism of anticipatory regulation. Recent work indicates that connections among the PHO regulon, Target of Rapamycin Complex 1 signaling, oxidative stress management, and cell wall construction are based both in direct signaling links, and in the provision of phosphate for sufficient metabolic intermediates that are substrates in these processes. Fundamental differences in fungal and human phosphate homeostasis may offer novel drug targets.
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18
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Tsay S, Williams SR, Benedict K, Beldavs Z, Farley M, Harrison L, Schaffner W, Dumyati G, Blackstock A, Guh A, Vallabhaneni S. A Tale of Two Healthcare-associated Infections: Clostridium difficile Coinfection Among Patients With Candidemia. Clin Infect Dis 2020; 68:676-679. [PMID: 30060067 DOI: 10.1093/cid/ciy607] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2018] [Accepted: 07/25/2018] [Indexed: 01/05/2023] Open
Abstract
Candidemia and Clostridium difficile infection (CDI) are important healthcare-associated infections that share certain risk factors. We sought to describe candidemia-CDI coinfection using population-based surveillance data. We found that nearly 1 in 10 patients with candidemia had CDI coinfection.
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Affiliation(s)
- Sharon Tsay
- Division of Foodborne, Waterborne, and Environmental Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia.,Epidemic Intelligence Service, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Sabrina R Williams
- Division of Foodborne, Waterborne, and Environmental Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Kaitlin Benedict
- Division of Foodborne, Waterborne, and Environmental Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Zintars Beldavs
- Oregon Health Authority, Portland.,Oregon Emerging Infections Program, Portland
| | - Monica Farley
- Emory University School of Medicine, Atlanta.,Georgia Emerging Infections Program, Atlanta
| | - Lee Harrison
- University of Pittsburgh, Pennsylvania.,Maryland Emerging Infections Program, Baltimore
| | - William Schaffner
- Vanderbilt University School of Medicine, Nashville.,Tennessee Emerging Infections Program, Nashville
| | - Ghinwa Dumyati
- University of Rochester Medical Center, Rochester.,New York Emerging Infections Program, Rochester
| | - Anna Blackstock
- Division of Foodborne, Waterborne, and Environmental Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Alice Guh
- Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Snigdha Vallabhaneni
- Division of Foodborne, Waterborne, and Environmental Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
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Candida Bloodstream Infection: Changing Pattern of Occurrence and Antifungal Susceptibility over 10 Years in a Tertiary Care Saudi Hospital. CANADIAN JOURNAL OF INFECTIOUS DISEASES & MEDICAL MICROBIOLOGY 2019; 2019:2015692. [PMID: 31929847 PMCID: PMC6935793 DOI: 10.1155/2019/2015692] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Revised: 09/12/2019] [Accepted: 11/06/2019] [Indexed: 01/04/2023]
Abstract
Background Candida has emerged as one of the most important pathogens that cause bloodstream infection (BSI).Understanding the current Candida BSI trends, the dominant species causing disease and the mortality associated with this infection are crucial to optimize therapeutic and prophylaxis measures. Objectives To study the epidemiology and to evaluate the risk factors, prognostic factors, and mortality associated with candidemia and to compare these findings with previously published studies from Saudi Arabia. Design A retrospective medical record review. Setting Tertiary hospital in Riyadh. Patients and Methods The analysis included all cases of Candida blood stream infection who are >18 years old over the period from 2013 to 2018. Continuous variables were compared using the parametric T-test while categorical variables were compared using the Chi-squared test. Main Outcome Measure Incidence, resistance, and hospital outcomes in Candida blood stream infection. Sample Size 324 patients. Results Three hundred and twenty-four episodes of Candida blood stream infections were identified. Median age of patients was 49.7 SD ± 28.1 years, and 53% of patients were males. More than half of the patients had an underlying disease involving the abdomen or laparotomy, 78% had an indwelling intravenous catheter, and 62% had suffered a bacterial infection within 2 weeks prior to candidemia. Candida albicans represents 33% of all isolates with decreasing trend overtime. There was an increase in the number of nonalbicans Candida overtime with Candida tropicalis in the lead (20%). Use of broad spectrum antibiotics (82%), prior ICU admission (60%) and use of central venous catheters (58%) were the most prevalent predisposing factors of candidemia. Azole resistance was variable overtime. Resistance to caspofungin remained very low (1.9%). Fourteen days crude mortality was 37% for ICU patients and 26.7% in non-ICU patients, while hospital crude mortality was 64.4% and 46.7%, respectively. Conclusion There is an increasing trend of nonalbicans Candida blood stream infection. Fluconazole resistance remained low to C. albicans. Most isolates remain susceptible to caspofungin, voriconazole, and amphotericin B. Candida bloodstream infection is associated with high 14-day hospital mortality.
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Summers KL, Frey JF, Ramsay TG, Arfken AM. The piglet mycobiome during the weaning transition: a pilot study1. J Anim Sci 2019; 97:2889-2900. [PMID: 31136650 DOI: 10.1093/jas/skz182] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Accepted: 05/24/2019] [Indexed: 12/12/2022] Open
Abstract
The importance of the microbiota in the gastrointestinal tract of animals is recognized as a critical player in host health. Recently, the significance of the mycobiome has been recognized, but culture-independent studies are limited, especially in swine. Weaning is a time of stress, dietary changes, and a predisposition to infections, making it a time point of interest to industry. In this pilot study, we sought to assess and characterize the mycobiome in the feces of swine from birth through the critical weaning transition to investigate the mycobiome population and its temporal dynamics in piglet feces. Cultured fecal samples demonstrate a significant increase in fungal burden following weaning that does not differ from adult levels, suggesting stable colonization. Culturable fungi were not found in any environmental samples tested, including water, food, sow milk or colostrum. To determine the fungal diversity present and to address the problem of unculturable fungi, we performed a pilot study utilizing ITS and 16S rRNA focused primers for high-throughput sequencing of fungal and bacterial species, respectively. Bacterial populations increase in diversity over the experimental timeline (days 1 to 35 postbirth), but the fungal populations do not demonstrate the same temporal trend. Following weaning, there is a dynamic shift in the feces to a Saccharomycetaceae-dominated population. The shift in fungal population was because of the dominance of Kazachstania slooffiae, a poorly characterized colonizer of animal gastrointestinal tracts. This study provides insights into the early colonization and subsequent establishment of fungi during the weaning transition in piglets. Future studies will investigate the effect of the mycobiome on piglet growth and health during the weaning transition.
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Affiliation(s)
- Katie L Summers
- Animal Biosciences and Biotechnology Laboratory, U.S. Department of Agriculture, Agricultural Research Service, Beltsville, MD
| | - Juli Foster Frey
- Animal Biosciences and Biotechnology Laboratory, U.S. Department of Agriculture, Agricultural Research Service, Beltsville, MD
| | - Timothy G Ramsay
- Animal Biosciences and Biotechnology Laboratory, U.S. Department of Agriculture, Agricultural Research Service, Beltsville, MD
| | - Ann M Arfken
- Animal Biosciences and Biotechnology Laboratory, U.S. Department of Agriculture, Agricultural Research Service, Beltsville, MD
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Fotedar V, Ganju S, Fotedar S, Thakur P, Sharma A, Bhardwaj V. Oral Microflora among Oral Cancer Patients Undergoing Radiotherapy in Regional Cancer Center, Indira Gandhi Medical College, Shimla. Indian J Med Paediatr Oncol 2019. [DOI: 10.4103/ijmpo.ijmpo_247_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Abstract
Objective: The objective of this study was to identify the microflora, especially Gram-positive, Gram-negative, and Candida species, in patients with oral squamous cell carcinoma during various stages from diagnosis through radiotherapy. Materials and Methods: A total of 17 cases with histological diagnosis of squamous cell carcinoma of the oral cavity were enrolled in the study. For each patient, the sample was collected thrice, i.e., at the time of diagnosis (Sample 1), 14th–15th day (Sample 2), and on the 29th–30th day of radiotherapy (Sample 3). The swab stick was rolled across the oral mucosa in the cases and was sent immediately to the Department of Microbiology, Indira Gandhi Medical College, Shimla, for processing. The swabs were inoculated on MacConkey agar, blood agar, and Sabouraud dextrose agar. After overnight incubation at 37°C, the organisms were identified by colony characteristics, catalase, coagulase test, Gram staining, and standard biochemical tests. Results: Out of 17, there was a loss to follow up in three patients, so after analyzing on 14 patients, we had 12 (85.7%) males and 2 (14.3%) females. The mean age of the population was 47.6% ± 12.2%. We had significantly higher proportion of Gram-positive microorganisms in Sample 1 as compared to Sample 3 and the same proportion of Gram-negative organisms in Sample 1 and Sample 3. Candida species was also proportionately higher in Sample 3 as compared to Sample 1. Conclusion: There is a shift of oral microflora from Gram-positive to Candida species from Sample 1 to Sample 3 and Gram-negative being same in Sample 1 and Sample 3.
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Affiliation(s)
- Vikas Fotedar
- Department of Radiation Oncology, Regional Cancer Center, Indira Gandhi Medical College, Shimla, Himachal Pradesh, India
| | - Suniti Ganju
- Department of Microbiology, Indira Gandhi Medical College, Shimla, Himachal Pradesh, India
| | - Shailee Fotedar
- Department of Public Health Dentistry, H. P. Government Dental College, Shimla, Himachal Pradesh, India
| | - Purnima Thakur
- Department of Radiation Oncology, Regional Cancer Center, Indira Gandhi Medical College, Shimla, Himachal Pradesh, India
| | - Aman Sharma
- Department of Radiation Oncology, Regional Cancer Center, Indira Gandhi Medical College, Shimla, Himachal Pradesh, India
| | - Vinay Bhardwaj
- Department of Public Health Dentistry, H. P. Government Dental College, Shimla, Himachal Pradesh, India
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22
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Stewart D, Romo JA, Lamendella R, Kumamoto CA. The role of fungi in C. difficile infection: An underappreciated transkingdom interaction. Fungal Genet Biol 2019; 129:1-6. [PMID: 30978391 DOI: 10.1016/j.fgb.2019.04.007] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2018] [Revised: 03/27/2019] [Accepted: 04/09/2019] [Indexed: 02/07/2023]
Abstract
Novel culture independent technologies have further elucidated the composition of the human mycobiome, though the role of fungi in human health and disease remains largely unknown. Recent studies have suggested conflicting roles for fungi in the gastrointestinal tract, underscoring the complexity of the interactions between the mycobiome, its bacterial counterpart, and the host. One key example is the observation that fungal taxa are overrepresented in patients with Clostridioides difficile infection (CDI), suggesting a role for fungi in this disease. Recent studies in murine models have demonstrated the ability of the commensal fungus Candida albicans to alter the course of CDI, supporting the notion that fungi play a role in this infection. This review summarizes current data on fungi and CDI, and shows that views of the dysbiotic state that is central to the pathogenesis of CDI are incomplete without consideration of the mycobiome.
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Affiliation(s)
- David Stewart
- Department of Surgery, University of Arizona, Tucson, AZ 85724, USA.
| | - Jesus A Romo
- Department of Molecular Biology and Microbiology, Tufts University, Boston, MA 02111, USA.
| | | | - Carol A Kumamoto
- Department of Molecular Biology and Microbiology, Tufts University, Boston, MA 02111, USA.
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23
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Synthetic gutomics: Deciphering the microbial code for futuristic diagnosis and personalized medicine. METHODS IN MICROBIOLOGY 2019. [DOI: 10.1016/bs.mim.2019.02.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Alka K, Amberkar VS, Mohan Kumar KP, Nandini DB, Vidyasagar B. Estimation of salivary Candida albicans counts in asthmatic adult patients taking anti-asthmatic medication for 3-5 years. J Oral Maxillofac Pathol 2018; 22:341-346. [PMID: 30651678 PMCID: PMC6306586 DOI: 10.4103/jomfp.jomfp_36_17] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2017] [Accepted: 06/15/2018] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND Bronchial asthma is a chronic inflammatory disease of airways. The disease itself along with the principal medication used makes the oral cavity susceptible to most common opportunistic infection, i.e., oral candidiasis. There are many species of Candida causing oral candidiasis, but the most prevalent among them is Candida albicans. Hence, assessing C. albicans count in response to disease and its treatment is necessary. This enables us to educate asthma patients about side effects of medication and highlight the necessity for oral health care, thereby improving their quality of life. AIMS The present study aims to evaluate the effects of asthma and its medication on C. albicans count in saliva samples of asthmatic adult patients taking medication for 3-5 years and compare C. albicans count in saliva samples among cases and controls. MATERIALS AND METHODS Thirty asthmatic adults taking medication for asthma since 3-5 years' age ranging from 20 to 50 years and equal number of age- and sex-matched healthy participants were included in the study. In both groups, saliva was collected and inoculated on Sabouraud Dextrose Agar culture plates for estimation of C. albicans counts. C. albicans counts were assessed in colony-forming unit/milliliter. STATISTICAL ANALYSIS Mann-Whitney U-test and Fisher's exact t-test were used. RESULTS The C. albicans count is significantly higher among asthmatics than healthy individuals. CONCLUSIONS The present study concludes that there is increased candidal growth among asthmatics as compared to their normal healthy counterpart.
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Affiliation(s)
- Kumari Alka
- Independent Researcher, Mysuru, Karnataka, India
| | - Vikram S Amberkar
- Department of Oral Pathology and Microbiology, College of Dental Sciences, Davangere, Karnataka, India
| | - K P Mohan Kumar
- Department of Oral Pathology and Microbiology, College of Dental Sciences, Davangere, Karnataka, India
| | - D B Nandini
- Department of Oral Pathology, Dental College, Regional Institute of Medical Science, Imphal, Manipur, India
| | - B Vidyasagar
- Department of Pulmonary Medicine, JJM Medical College and Hospital, Davangere, Karnataka, India
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25
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Zhang I, Pletcher SD, Goldberg AN, Barker BM, Cope EK. Fungal Microbiota in Chronic Airway Inflammatory Disease and Emerging Relationships with the Host Immune Response. Front Microbiol 2017; 8:2477. [PMID: 29312187 PMCID: PMC5733051 DOI: 10.3389/fmicb.2017.02477] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2017] [Accepted: 11/29/2017] [Indexed: 12/22/2022] Open
Abstract
The respiratory tract is a complex system that is inhabited by niche-specific communities of microbes including bacteria, fungi, and viruses. These complex microbial assemblages are in constant contact with the mucosal immune system and play a critical role in airway health and immune homeostasis. Changes in the composition and diversity of airway microbiota are frequently observed in patients with chronic inflammatory diseases including chronic rhinosinusitis (CRS), cystic fibrosis, allergy, and asthma. While the bacterial microbiome of the upper and lower airways has been the focus of many recent studies, the contribution of fungal microbiota to inflammation is an emerging research interest. Within the context of allergic airway disease, fungal products are important allergens and fungi are potent inducers of inflammation. In addition, murine models have provided experimental evidence that fungal microbiota in peripheral organs, notably the gastrointestinal (GI) tract, influence pulmonary health. In this review, we explore the role of the respiratory and GI microbial communities in chronic airway inflammatory disease development with a specific focus on fungal microbiome interactions with the airway immune system and fungal-bacterial interactions that likely contribute to inflammatory disease. These findings are discussed in the context of clinical and immunological features of fungal-mediated disease in CRS, allergy, and asthmatic patients. While this field is still nascent, emerging evidence suggests that dysbiotic fungal and bacterial microbiota interact to drive or exacerbate chronic airway inflammatory disease.
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Affiliation(s)
- Irene Zhang
- Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, United States
| | - Steven D. Pletcher
- Department of Otolaryngology Head and Neck Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - Andrew N. Goldberg
- Department of Otolaryngology Head and Neck Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - Bridget M. Barker
- Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, United States
| | - Emily K. Cope
- Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, United States
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26
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The Fungal Mycobiome and Its Interaction with Gut Bacteria in the Host. Int J Mol Sci 2017; 18:ijms18020330. [PMID: 28165395 PMCID: PMC5343866 DOI: 10.3390/ijms18020330] [Citation(s) in RCA: 137] [Impact Index Per Article: 17.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2016] [Revised: 01/05/2017] [Accepted: 01/25/2017] [Indexed: 12/12/2022] Open
Abstract
The advent of sequencing technology has endowed us with the capacity to study microbes constituting the human commensal community that were previously non-culturable. Much of the initial works have concentrated on the bacterial flora constituting the gut microbiome, since specimens are readily accessible in health and disease. Less, however, is understood of the “silent population”—the fungal species, also known as the mycobiome. Living in symbiosis with bacteria as commensals in our body, it is perceivable that the mycobiome exerts an inadvertent influence on the microbiome. We review here the recent knowledge gained from study of the interaction between the mycobiome and microbiome in health and disease susceptibility, immunity, and consequences from antimicrobial treatment.
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Abstract
Many species of fungi have been detected in the healthy human gut; however, nearly half of all taxa reported have only been found in one sample or one study. Fungi capable of growing in and colonizing the gut are limited to a small number of species, mostly Candida yeasts and yeasts in the family Dipodascaceae (Galactomyces, Geotrichum, Saprochaete). Malassezia and the filamentous fungus Cladosporium are potential colonizers; more work is needed to clarify their role. Other commonly-detected fungi come from the diet or environment but either cannot or do not colonize (Penicillium and Debaryomyces species, which are common on fermented foods but cannot grow at human body temperature), while still others have dietary or environmental sources (Saccharomyces cerevisiae, a fermentation agent and sometime probiotic; Aspergillus species, ubiquitous molds) yet are likely to impact gut ecology. The gut mycobiome appears less stable than the bacterial microbiome, and is likely subject to environmental factors.
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Affiliation(s)
- Heather E Hallen-Adams
- a Department of Food Science and Technology , University of Nebraska , Lincoln , NE , USA
| | - Mallory J Suhr
- a Department of Food Science and Technology , University of Nebraska , Lincoln , NE , USA
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Uppal B, Panda PS, Kishor S, Sharma S, Farooqui FH. Speciation of Candida isolates obtained from diarrheal stool. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2016. [DOI: 10.4103/1110-7782.193888] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Zhang J, Hung GC, Nagamine K, Li B, Tsai S, Lo SC. Development of Candida-Specific Real-Time PCR Assays for the Detection and Identification of Eight Medically Important Candida Species. Microbiol Insights 2016; 9:21-8. [PMID: 27103821 PMCID: PMC4836890 DOI: 10.4137/mbi.s38517] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2016] [Revised: 02/17/2016] [Accepted: 02/19/2016] [Indexed: 11/28/2022] Open
Abstract
Culture-based identification methods have been the gold standard for the diagnosis of fungal infection. Currently, molecular technologies such as real-time PCR assays with short turnaround time can provide desirable alternatives for the rapid detection of Candida microbes. However, most of the published PCR primer sets are not Candida specific and likely to amplify DNA from common environmental contaminants, such as Aspergillus microbes. In this study, we designed pan-Candida primer sets based on the ribosomal DNA-coding regions conserved within Candida but distinct from those of Aspergillus and Penicillium. We demonstrate that the final two selected pan-Candida primer sets would not amplify Aspergillus DNA and could be used to differentiate eight medically important Candida pathogens in real-time PCR assays based on their melting profiles, with a sensitivity of detection as low as 10 fg of Candida genomic DNA. Moreover, we further evaluated and selected species-specific primer sets covering Candida albicans, Candida glabrata, Candida tropicalis, and Candida dubliniensis and show that they had high sensitivity and specificity. These real-time PCR primer sets could potentially be assembled into a single PCR array for the rapid detection of Candida species in various clinical settings, such as corneal transplantation.
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Affiliation(s)
- Jing Zhang
- Tissue Microbiology Laboratory, Division of Cellular and Gene Therapies, Office of Cellular, Tissue and Gene Therapies, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA
| | - Guo-Chiuan Hung
- Tissue Microbiology Laboratory, Division of Cellular and Gene Therapies, Office of Cellular, Tissue and Gene Therapies, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA
| | - Kenjiro Nagamine
- Tissue Microbiology Laboratory, Division of Cellular and Gene Therapies, Office of Cellular, Tissue and Gene Therapies, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.; Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan
| | - Bingjie Li
- Tissue Microbiology Laboratory, Division of Cellular and Gene Therapies, Office of Cellular, Tissue and Gene Therapies, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA
| | - Shien Tsai
- Tissue Microbiology Laboratory, Division of Cellular and Gene Therapies, Office of Cellular, Tissue and Gene Therapies, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA
| | - Shyh-Ching Lo
- Tissue Microbiology Laboratory, Division of Cellular and Gene Therapies, Office of Cellular, Tissue and Gene Therapies, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.; Senior Investigator, Medical Officer, Tissue Microbiology Laboratory, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA
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Jain M, Shah R, Chandolia B, Mathur A, Chauhan Y, Chawda J, Mosby S, Bhagalia S. The Oral Carriage of Candida in Oral Cancer Patients of Indian Origin Undergoing Radiotherapy and/or Chemotherapy. J Clin Diagn Res 2016; 10:ZC17-20. [PMID: 27042578 DOI: 10.7860/jcdr/2016/15702.7180] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Accepted: 12/19/2015] [Indexed: 11/24/2022]
Abstract
INTRODUCTION Oral cancer is a challenging disease in Indian subcontinent because of increased use of tobacco and associated products. Although surgery is the main treatment modality, radiotherapy (RT) and chemotherapy (CT) are employed in inaccessible cases. Both RT & CT will result in painful and debilitating adverse effects in oral cavity e.g., mucositis, ulceration, dysgeusia, xerostomia and opportunistic infections. One of the most common opportunistic infection is caused by fungus Candida. AIM Our aim was to investigate the incidence of oral colonization of Candida species with differentiation between carrier and infective state of the organism. We also investigate the effect of treatment modality (RT and CT) on the incidence of Candida, in oral cancer patients, undergoing RT and/or CT, in order to prevent and treat the Candida infection in a better way. MATERIALS AND METHODS It was a cross-sectional case-control study; done in Gujarat, India. Fifty patients of oral cancer undergoing RT, CT alone or combined were investigated and compared with the healthy controls. The samples were collected from mid-dorsum of tongue by using imprint culture technique. The samples were inoculated on Sabouraud's dextrose agar medium and the organisms were identified by wet mount, germ tube test, chlamydospore formation and sugar fermentation tests. RESULTS There was significant increase in oral Candida colonization from 20% in healthy controls to 70% in oral cancer patients undergoing RT and/or CT (p = 0.001, < 0.05). A significant increase in infective state of Candida (71.4%) was noted (p = 0.001, < 0.05) with predominance of non-albicans species of Candida, chiefly C. tropicalis (42.8%). CONCLUSION RT and CT leads to increased oral colonization and infection by Candida with a shift towards growth of non-albicans species. As the pattern of candidal species infection is changing, such studies are important for better diagnosis and treatment planning to gain good control over the disease.
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Affiliation(s)
- Manish Jain
- Associate Professor, Department of Oral and Maxillofacial Pathology, NIMS Dental College , Jaipur, India
| | - Raksha Shah
- Professor and Ex HOD, Department of Oral and Maxillofacial Pathology, Government Dental College and Hospital , Ahmadabad, India
| | - Betina Chandolia
- Senior Lecturer, Department of Oral and Maxillofacial Pathology, NIMS Dental College , Jaipur, India
| | - Ayush Mathur
- Senior Lecturer, Department of Orthodontics, NIMS Dental College , Jaipur, India
| | - Yashwant Chauhan
- Senior Lecturer, Department of Pedodontics, NIMS Dental College , Jaipur, India
| | - Jyoti Chawda
- Professor and HOD, Department of Oral and Maxillofacial Pathology, Government Dental College and Hospital , Ahmadabad, India
| | - Siddarth Mosby
- Professor and Ex HOD, Department of Oral and Maxillofacial Pathology, NIMS Dental College , Jaipur, India
| | - Sanjay Bhagalia
- Professor and Ex HOD, Department of Oral and Maxillofacial Pathology, NIMS Dental College , Jaipur, India
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Forrester JD, Gomez CA, Forrester JA, Nguyen M, Gregg D, Deresinski S, Banaei N, Weiser TG. First case of mesh infection due to Coccidioides spp. and literature review of fungal mesh infections after hernia repair. Mycoses 2015; 58:582-7. [PMID: 26293423 DOI: 10.1111/myc.12364] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2015] [Revised: 06/02/2015] [Accepted: 06/30/2015] [Indexed: 12/13/2022]
Abstract
Fungal mesh infections are a rare complication of hernia repairs with mesh. The first case of Coccidioides spp. mesh infection is described, and a systematic literature review of all known fungal mesh infections was performed. Nine cases of fungal mesh infection are reviewed. Female and male patients are equally represented, median age is 49.5 years, and critical illness and preinfection antibiotic use were common. Fungal mesh infections are rare, but potentially fatal, complications of hernias repaired with mesh.
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Affiliation(s)
| | - Carlos A Gomez
- Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, CA, USA
| | | | - Mike Nguyen
- Department of Pathology, Stanford University, Palo Alto, CA, USA
| | - David Gregg
- Department of Surgery, Stanford University, Stanford, CA, USA
| | - Stan Deresinski
- Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, CA, USA
| | - Niaz Banaei
- Clinical Microbiology Laboratory, Stanford University, Palo Alto, CA, USA
| | - Thomas G Weiser
- Department of Surgery, Stanford University, Stanford, CA, USA
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Abstract
Small intestinal fungal overgrowth (SIFO) is characterized by the presence of excessive number of fungal organisms in the small intestine associated with gastrointestinal (GI) symptoms. Candidiasis is known to cause GI symptoms particularly in immunocompromised patients or those receiving steroids or antibiotics. However, only recently, there is emerging literature that an overgrowth of fungus in the small intestine of non-immunocompromised subjects may cause unexplained GI symptoms. Two recent studies showed that 26 % (24/94) and 25.3 % (38/150) of a series of patients with unexplained GI symptoms had SIFO. The most common symptoms observed in these patients were belching, bloating, indigestion, nausea, diarrhea, and gas. The underlying mechanism(s) that predisposes to SIFO is unclear but small intestinal dysmotility and use of proton pump inhibitors has been implicated. However, further studies are needed; both to confirm these observations and to examine the clinical relevance of fungal overgrowth, both in healthy subjects and in patients with otherwise unexplained GI symptoms. Importantly, whether eradication or its treatment leads to resolution of symptoms remains unclear; at present, a 2-3-week course of antifungal therapy is recommended and may be effective in improving symptoms, but evidence for eradication is lacking.
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Affiliation(s)
- Askin Erdogan
- Section of Gastroenterology and Hepatology, Georgia Regents University, Augusta, GA, USA
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α-Mannan induces Th17-mediated pulmonary graft-versus-host disease in mice. Blood 2015; 125:3014-23. [PMID: 25740827 DOI: 10.1182/blood-2014-12-615781] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2014] [Accepted: 02/23/2015] [Indexed: 12/11/2022] Open
Abstract
Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative therapy for various hematopoietic disorders. Graft-versus-host disease (GVHD) and infections are the major obstacles of HSCT, and their close relationship has been suggested. Although roles of bacterial and viral infections in the pathophysiology of GVHD are well described, impacts of fungal infection on GVHD remain to be elucidated. In mouse models of GVHD, injection of α-mannan (Mn), a major component of fungal cell wall, or heat-killed Candida albicans exacerbated GVHD, particularly in the lung. Mn-induced donor T-cell polarization toward Th17 and lung-specific chemokine environment in GVHD led to accumulation of Th17 cells in the lung. The detrimental effects of Mn on GVHD depended on donor IL-17A production and host C-type lectin receptor Dectin-2. These results suggest a previously unrecognized link between pulmonary GVHD and fungal infection after allogeneic HSCT.
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Abstract
Fungi are pathogens that commonly infect immunocompromised patients and can affect any organs of the body, including the colon. However, the literature provides limited details on colonic infections caused by fungi. This article is an intensive review of information available on the fungi that can cause colon infections. It uses a comparative style so that its conclusions may be accessible for clinical application.
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Affiliation(s)
- Surat Praneenararat
- Division of Gastroenterology, Department of Medicine, Prince of Songkla University, Songkhla, Thailand
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35
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Raponi G, Visconti V, Brunetti G, Ghezzi MC. Clostridium difficile Infection and Candida Colonization of the Gut: Is There a Correlation? Clin Infect Dis 2014; 59:1648-9. [DOI: 10.1093/cid/ciu637] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
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36
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Kim YG, Udayanga KGS, Totsuka N, Weinberg JB, Núñez G, Shibuya A. Gut dysbiosis promotes M2 macrophage polarization and allergic airway inflammation via fungi-induced PGE₂. Cell Host Microbe 2014; 15:95-102. [PMID: 24439901 DOI: 10.1016/j.chom.2013.12.010] [Citation(s) in RCA: 281] [Impact Index Per Article: 25.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2013] [Revised: 10/02/2013] [Accepted: 12/24/2013] [Indexed: 11/16/2022]
Abstract
Although imbalances in gut microbiota composition, or "dysbiosis," are associated with many diseases, the effects of gut dysbiosis on host systemic physiology are less well characterized. We report that gut dysbiosis induced by antibiotic (Abx) treatment promotes allergic airway inflammation by shifting macrophage polarization in the lung toward the alternatively activated M2 phenotype. Adoptive transfer of alveolar macrophages derived from Abx-treated mice was sufficient to increase allergic airway inflammation. Abx treatment resulted in the overgrowth of a commensal fungal Candida species in the gut and increased plasma concentrations of prostaglandin E₂ (PGE₂), which induced M2 macrophage polarization in the lung. Suppression of PGE₂ synthesis by the cyclooxygenase inhibitors aspirin and celecoxib suppressed M2 macrophage polarization and decreased allergic airway inflammatory cell infiltration in Abx-treated mice. Thus, Abx treatment can cause overgrowth of particular fungal species in the gut and promote M2 macrophage activation at distant sites to influence systemic responses including allergic inflammation.
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Affiliation(s)
- Yun-Gi Kim
- Department of Immunology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan; Japan Science and Technology Agency, Core Research for Evolutional Science and Technology (CREST), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan; Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA
| | - Kankanam Gamage Sanath Udayanga
- Department of Immunology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan; Japan Science and Technology Agency, Core Research for Evolutional Science and Technology (CREST), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
| | - Naoya Totsuka
- Department of Immunology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan; Japan Science and Technology Agency, Core Research for Evolutional Science and Technology (CREST), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
| | - Jason B Weinberg
- Department of Pediatrics and Communicable Diseases, Microbiology, and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
| | - Gabriel Núñez
- Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA
| | - Akira Shibuya
- Department of Immunology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan; Japan Science and Technology Agency, Core Research for Evolutional Science and Technology (CREST), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan; Life Science Center of Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
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Martínez-Ramírez JA, Walther G, Peters FT. Studies on drug metabolism by fungi colonizing decomposing human cadavers. Part II: biotransformation of five model drugs by fungi isolated from post-mortem material. Drug Test Anal 2014; 7:265-79. [DOI: 10.1002/dta.1669] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2014] [Revised: 04/12/2014] [Accepted: 04/12/2014] [Indexed: 11/10/2022]
Affiliation(s)
- Jorge A. Martínez-Ramírez
- Institute of Forensic Medicine; Jena University Hospital; Fürstengraben 23 D-07743 Jena Germany
- Department of Pharmacy; National University; A.A. 14490 Bogotá D.C. Colombia
| | - Grit Walther
- Institute of Microbiology, Department of Microbiology and Molecular Biology; University of Jena; Neugasse 25 D-07743 Jena Germany
- Leibniz-Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute; Jena Microbial Resource Collection; Beutenbergstr. 11a 07745 Jena Germany
| | - Frank T. Peters
- Institute of Forensic Medicine; Jena University Hospital; Fürstengraben 23 D-07743 Jena Germany
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Studies on drug metabolism by fungi colonizing decomposing human cadavers. Part I: DNA sequence-based identification of fungi isolated from postmortem material. Anal Bioanal Chem 2013; 405:8443-50. [DOI: 10.1007/s00216-013-7250-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2013] [Revised: 07/09/2013] [Accepted: 07/11/2013] [Indexed: 11/26/2022]
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Manian FA, Bryant A. Does Candida species overgrowth protect against Clostridium difficile infection? Clin Infect Dis 2012; 56:464-5. [PMID: 23042967 DOI: 10.1093/cid/cis854] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
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40
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Sasaki K. Candida-associated gastric ulcer relapsing in a different position with a different appearance. World J Gastroenterol 2012; 18:4450-3. [PMID: 22969213 PMCID: PMC3436065 DOI: 10.3748/wjg.v18.i32.4450] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2012] [Revised: 08/07/2012] [Accepted: 08/14/2012] [Indexed: 02/06/2023] Open
Abstract
An 87-year-old, Japanese woman was shown to have a submucosal tumor-like lesion with a deep, central ulceration covered with thick, whitish exudate in the stomach. Biopsy showed Candida tropicalis but not Helicobacter pylori (H. pylori). She had no predisposing factors or history of peptic ulcers nor had taken non-steroidal anti-inflammatory drugs (NSAIDs), diagnosed with Candida-associated gastric ulcer. Though cured of the lesion, she developed another ulcer in a different position, in which Candida was demonstrated but H. pylori was undetectable. This is the first case of recurrent Candida-associated gastric ulcer in the world. Detected in both the original and recurrent lesions in an H. pylori-negative patient with no antecedent ulcers who had not taken NSAIDs, Candida is considered, contrary to the prevailing opinion, to play an etiologic role in ulcer formation.
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N-acetylglucosamine induces white-to-opaque switching and mating in Candida tropicalis, providing new insights into adaptation and fungal sexual evolution. EUKARYOTIC CELL 2012; 11:773-82. [PMID: 22544905 DOI: 10.1128/ec.00047-12] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Pathogenic fungi are capable of switching between different phenotypes, each of which has a different biological advantage. In the most prevalent human fungal pathogen, Candida albicans, phenotypic transitions not only improve its adaptation to a continuously changing host microenvironment but also regulate sexual mating. In this report, we show that Candida tropicalis, another important human opportunistic pathogen, undergoes reversible and heritable phenotypic switching, referred to as the "white-opaque" transition. Here we show that N-acetylglucosamine (GlcNAc), an inducer of white-to-opaque switching in C. albicans, promotes opaque-cell formation and mating and also inhibits filamentation in a number of natural C. tropicalis strains. Our results suggest that host chemical signals may facilitate this phenotypic switching and mating of C. tropicalis, which had been previously thought to reproduce asexually. Overexpression of the C. tropicalis WOR1 gene in C. albicans induces opaque-cell formation. Additionally, an intermediate phase between white and opaque was observed in C. tropicalis, indicating that the switching could be tristable.
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Yoo H, Chung CS, Jung SW, Moh IH, Song W, Lee J. A Case of Delayed Onset Chest Wall Abscess after Candidemia. Infect Chemother 2012. [DOI: 10.3947/ic.2012.44.3.188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Affiliation(s)
- Hana Yoo
- Department of Internal Medicine, College of Medicine, Hallym University, Seoul, Korea
| | - Chang Su Chung
- Department of Internal Medicine, College of Medicine, Hallym University, Seoul, Korea
| | - Sung Woong Jung
- Department of Internal Medicine, College of Medicine, Hallym University, Seoul, Korea
| | - In Ho Moh
- Department of Internal Medicine, College of Medicine, Hallym University, Seoul, Korea
| | - WonKeun Song
- Department of Laboratory Medicine, College of Medicine, Hallym University, Seoul, Korea
| | - Jacob Lee
- Department of Internal Medicine, College of Medicine, Hallym University, Seoul, Korea
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Kantheti LPC, Reddy BVR, Ravikumar S, Anuradha CH, Chandrasekhar P, Rajeswari MR. Isolation, identification, and carriage of candidal species in PHLAs and their correlation with immunological status in cases with and without HAART. J Oral Maxillofac Pathol 2012; 16:38-44. [PMID: 22438641 PMCID: PMC3303520 DOI: 10.4103/0973-029x.92971] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
AIMS AND OBJECTIVES To know the prevalence of Candidal colonization, and to isolate and know the Candidal species prevalent in the oral cavity from the oral rinse samples collected from the individuals attending to the Voluntary Counseling and Confidential Testing Center (VCCTC) and the antiretro-viral therapy (ART) Center at Government General Hospital, Guntur, Andhra Pradesh, South India. MATERIALS AND METHODS The study group consisted of 50 HIV negative asymptomatic individuals (Group I); 50 HIV positive individuals (people living with HIV AIDS [PLWHA's]), who are naïve to antiretro-viral therapy (direct walk-in clients of VCCTC) (Group II); and 50 HIV positive individuals with CD4+ count less than 250 and who are started on highly active anti retroviral therapy (HAART) (Group III). Routine mycological tests for the isolation of pure cultures of Candida and also the speciation procedures were done. RESULTS In the study group, 53 (Group I=11; Group II=23; Group III=19) were culture positive. The prevalence of Candida was comparatively high in the age range between 41-50 years in Group II; 51-60 years, in Group III. A male predominance was observed in the Group I (M:F=16:6) and Group III (M:F=20:18), with a slight female predominance in the Group II (F:M=24:22). The overall culture positivity was 35.3%. Candida albicans was the highest prevalent species (47.17% of the isolates). A comparison of the culture positivity with the CD(4) counts of the study subjects was statistically highly significant. A pair wise comparison of the culture positivity with that of the colony forming units/mL from the subjects showed a high significance between Group I and Group II, and between Group I and Group III. CONCLUSION Candidal infections in immuno compromised patients are often severe, rapidly progressive, and difficult to treat and such patients have a definitive risk of developing oral candidiasis wherein, even the members of the normal oral flora may become pathogenic. Candida albicans is the common isolate. Nonalbicans species are also emerging as opportunistic pathogens. In view of this changing pattern, it is strongly recommended that species identification can help in much better treatment strategies, and thus, gain a good control over the disease. The findings of this study would be helpful in any further studies which, if done prospectively on a larger cohort, can be confirmatory.
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Affiliation(s)
| | - BVR Reddy
- Department of Oral Pathology, SIBAR Institute of Dental Sciences, Takkellapadu, India
| | - Shamala Ravikumar
- Department of Oral Pathology, SIBAR Institute of Dental Sciences, Takkellapadu, India
| | - CH Anuradha
- Department of Oral Pathology, SIBAR Institute of Dental Sciences, Takkellapadu, India
| | - P Chandrasekhar
- Department of Oral Pathology, SIBAR Institute of Dental Sciences, Takkellapadu, India
| | - M Raja Rajeswari
- Department of Microbiology, Guntur Medical College, Andhra Pradesh, India
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Mansueto P, Pisciotta G, Tomasello G, Cabibi D, Seidita A, D'Alcamo A, Patti AM, Sprini D, Carroccio A, Rini GB, Fede GD. Malignant tumor-like gastric lesion due to Candida albicans in a diabetic patient treated with cyclosporin: a case report and review of the literature. Clin Exp Med 2011; 12:201-5. [PMID: 21904834 DOI: 10.1007/s10238-011-0158-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2011] [Accepted: 08/26/2011] [Indexed: 11/29/2022]
Abstract
The gastrointestinal tract of healthy individuals is colonized by hundreds of saprophytes and mycetes, especially the Candida species, are habitual ones. Under certain conditions, the fungal flora may overgrow, resulting in lesions of the digestive mucosa which, rarely, can have a local diffusion and/or spread to the lympho-hematogenous system. Mycotic infections of the stomach can sometimes look like benign gastric ulcers. Here, we present the case report of a woman, aged 64, who presented with type II diabetes mellitus and psoriasis, on chronic treatment with cyclosporin A and with endoscopic evidence of an ulcerated, vegetating gastric lesion secondary to Candida albicans infection. Although strongly suggestive of malignancy, it completely healed after cyclosporin withdrawal and the administration of oral antifungal drugs.
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Affiliation(s)
- Pasquale Mansueto
- Internal Medicine, Department of Clinical Medicine and Emerging Diseases, University Hospital of Palermo, Via del Vespro, 141-90146, Palermo, Italy.
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Abstract
This is a case report on a 35-year-old man with acute myelogenous leukemia who presented fever and intermittent mucoid loose stool to the emergency center. He had been taking voriconazole for invasive pulmonary aspergillosis. The flexible sigmoidoscopy was consistent with the diagnosis of pseudomembranous colitis.
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Affiliation(s)
- Jae-Cheol Kwon
- The Hematopoietic Stem Cell Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Min-Kyu Kang
- The Hematopoietic Stem Cell Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Si-Hyun Kim
- The Hematopoietic Stem Cell Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Su-Mi Choi
- The Hematopoietic Stem Cell Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hee-Je Kim
- The Hematopoietic Stem Cell Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Woo-Sung Min
- The Hematopoietic Stem Cell Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Dong-Gun Lee
- The Hematopoietic Stem Cell Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Abstract
Severe acute pancreatitis (SAP) is associated with significant morbidity and mortality. The majority of deaths related to SAP are the result of infectious complications. Although bacterial infections are most commonly encountered, fungal infections are increasingly being recognized. Candida is the most common fungal infection. The occurrence of fungal infection in patients with acute pancreatitis adversely affects the clinical course, leading to a higher incidence of systemic complications, and possibly mortality as well. Important risk factors for fungal infection in patients with acute pancreatitis include broad-spectrum antibiotics, prolonged hospitalization and surgical/endoscopic interventions, use of total parenteral nutrition, and mechanical ventilation. Patients with higher severity of pancreatitis are at a greater risk. The pathogenesis of fungal infection in patients with acute pancreatitis is multifactorial. Translocation of microorganisms across the gut epithelium, lymphocyte dysfunction, and the virulence of the invading microorganisms play important roles. Histological demonstration of fungi remains the gold standard of diagnosis, but a positive biopsy is rarely obtained. The role of biomarkers in the diagnosis is being investigated. As early diagnosis and treatment can lead to improved outcome, a high index of suspicion is required for prompt diagnosis. Limiting the use of broad-spectrum antibiotics, early introduction of enteral nutrition, and timely change of vascular catheters are important preventive strategies. The role of antifungal prophylaxis remains controversial. Surgical necrosectomy with antifungal therapy is the most widely used treatment approach. Clinical trials on antifungal prophylaxis are needed, and indications for surgical intervention need to be clearly defined.
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Affiliation(s)
- Rakesh Kochhar
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
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Spanakis EK, Kourkoumpetis TK, Livanis G, Peleg AY, Mylonakis E. Statin therapy and decreased incidence of positive Candida cultures among patients with type 2 diabetes mellitus undergoing gastrointestinal surgery. Mayo Clin Proc 2010; 85:1073-9. [PMID: 21123633 PMCID: PMC2996154 DOI: 10.4065/mcp.2010.0447] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
OBJECTIVE To assess whether statin therapy decreases the incidence of cultures positive for Candida species among high-risk hospitalized patients with type 2 diabetes mellitus (DM). PATIENTS AND METHODS We performed a retrospective cohort study analyzing the records of all patients with type 2 DM who were admitted to Massachusetts General Hospital for lower gastrointestinal tract surgery between January 1, 2001, and May 1, 2008. We defined statin exposure as the filling of at least 1 prescription of statins during the 6 months before hospitalization or during the current hospital stay. The primary outcome was a culture positive for Candida species during hospitalization. Clinical information on a wide range of covariates was collected. Logistic regression analysis was used to adjust for possible confounders. RESULTS Of the 1019 patients who were eligible for the study, 493 (48%) were receiving statins. A total of 139 patients (14%) had at least 1 culture positive for Candida species during hospitalization. An adjusted multivariate model based on a backward stepwise elimination procedure showed that statin therapy significantly decreased the incidence of cultures positive for Candida species (odds ratio, 0.60; 95% confidence interval [CI], 0.38-0.96; P=.03) with a statistically significant prolonged time to event compared with no statin therapy (adjusted hazard ratio, 0.62; 95% CI, 0.44-0.88; P=.01). The benefit of statins was more prominent in patients with type 2 DM who had greater comorbidities (Charlson Comorbidity Index ≥2) (adjusted odds ratio, 0.47; 95% CI, 0.27-0.79; P=.01). CONCLUSION Among patients with type 2 DM who underwent gastrointestinal surgery, use of statins correlated with a decreased incidence of cultures positive for Candida species.
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Affiliation(s)
- Elias K. Spanakis
- From the Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Boston (E.K.S., T.K.K., E.M.); Department of Internal Medicine, Caritas St Elizabeth's Medical Center, Boston MA (E.K.S.); College of Business Administration, Northeastern University, Boston, MA (G.L.); and Department of Infectious Diseases, Alfred Hospital, and Department of Microbiology, Monash University, Melbourne, Australia, and Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, MA (A.Y.P.)
| | | | | | | | - Eleftherios Mylonakis
- From the Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Boston (E.K.S., T.K.K., E.M.); Department of Internal Medicine, Caritas St Elizabeth's Medical Center, Boston MA (E.K.S.); College of Business Administration, Northeastern University, Boston, MA (G.L.); and Department of Infectious Diseases, Alfred Hospital, and Department of Microbiology, Monash University, Melbourne, Australia, and Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, MA (A.Y.P.)
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Lee JA, Chee HY. In Vitro Antifungal Activity of Equol against Candida albicans. MYCOBIOLOGY 2010; 38:328-330. [PMID: 23956675 PMCID: PMC3741528 DOI: 10.4489/myco.2010.38.4.328] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/01/2010] [Accepted: 08/17/2010] [Indexed: 06/02/2023]
Abstract
In this study, we demonstrate that equol has fungicidal activities against Candida albicans. The minimum inhibitory and minimum fungicidal concentrations of equol against C. albicans were 516 and 1,032 µM, respectively. Two separate viability assays found that equol changed the integrity of the C. albicans cell membrane, possibly by formation of membrane lesions. Scanning electron microscopy demonstrated ultrastructural changes.
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Affiliation(s)
- Jeong Ah Lee
- Department of Cell Biology, College of Medicine, Konyang University, Daejeon 302-718, Korea
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Singhi S, Deep A. Invasive candidiasis in pediatric intensive care units. Indian J Pediatr 2009; 76:1033-44. [PMID: 19907936 DOI: 10.1007/s12098-009-0219-6] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2007] [Accepted: 08/27/2008] [Indexed: 01/28/2023]
Abstract
Candidemia and disseminated candidiasis are major causes of morbidity and mortality in hospitalized patients especially in the intensive care units (ICU). The incidence of invasive candidasis is on a steady rise because of increasing use of multiple antibiotics and invasive procedures carried out in the ICUs. Worldwide there is a shifting trend from C. albicans towards non albicans species, with an associated increase in mortality and antifungal resistance. In the ICU a predisposed host in one who is on broad spectrum antibiotics, parenteral nutrition, and central venous catheters. There are no pathognomonic signs or symptoms. The clinical clues are: unexplained fever or signs of severe sepsis or septic shock while on antibiotics, multiple, non-tender, nodular erythematous cutaneous lesions. The spectrum of infection with candida species range from superficial candidiasis of the skin and mucosa to more serious life threatening infections. Treatment of candidiasis involves removal of the most likely source of infection and drug therapy to speed up the clearance of infection. Amphotericin B remains the initial drug of first choice in hemodynamically unstable critically ill children in the wake of increasing resistance to azoles. Evaluation of newer antifungal agents and precise role of prophylactic therapy in ICU patients is needed.
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Affiliation(s)
- Sunit Singhi
- Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
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50
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Naggie S, Perfect JR. Molds: hyalohyphomycosis, phaeohyphomycosis, and zygomycosis. Clin Chest Med 2009; 30:337-53, vii-viii. [PMID: 19375639 DOI: 10.1016/j.ccm.2009.02.009] [Citation(s) in RCA: 55] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Emerging fungi previously thought to be nonpathogenic are now recognized as playing a significant role in the increased incidence of invasive fungal disease. This change in the epidemiology of invasive fungal infections (IFIs) has occurred in the era of aggressive new therapies for hematopoietic stem cell transplantation and other malignancies that lead to profound immunosuppression for longer durations and has extended the survival of these critically ill patients. The significant morbidity and mortality associated with these infections is not only related to the host populations but to delayed recognition and diagnosis and high rates of resistance in some of these emerging pathogens to standard antifungal therapies.
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Affiliation(s)
- Susanna Naggie
- Division of Infectious Diseases, Department of Internal Medicine, Duke University Medical Center, Durham, NC 27710, USA.
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