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Liu J, Chen S, Zhao J. The role and mechanisms of Helicobacter pylori outer membrane vesicles in the pathogenesis of extra-gastrointestinal diseases. Microb Pathog 2025; 200:107312. [PMID: 39855489 DOI: 10.1016/j.micpath.2025.107312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Revised: 12/20/2024] [Accepted: 01/18/2025] [Indexed: 01/27/2025]
Abstract
Helicobacter pylori (H. pylori) infection have been closely associated with several extra-gastrointestinal disorders. Outer membrane vesicles (OMVs), as lipid-membrane-bounded nanoparticles, are usually shed from Gram-negative both in vitro and in vivo. H. pylori is also capable of producing OMVs, which can enter the systemic circulation and be delivered to various cells, tissues or organs, eliciting a range of inflammatory and immune modulation responses. In this current review, we summarize the biogenesis and functions of H. pylori OMVs, describe the contribution of H. pylori OMVs to the generation and progression of extra-gastrointestinal diseases, such as neuronal damage, Alzheimer disease, hepatic fibrosis and atherosclerosis. We also explored the effect of H. pylori OMVs in inflammatory and immune modulation of diverse immune cells, including macrophages, mononuclear cells and dendritic cells. By elucidating the molecular mechanism of H. pylori OMVs-mediated extra-gastrointestinal diseases and immunomodulatory effect, it may promote the development of efficient treatments and vaccinations against H. pylori.
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Affiliation(s)
- Jin Liu
- Department of Pharmaceutical Engineering, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, 510006, People's Republic of China
| | - Sheqing Chen
- Department of Pharmaceutical Engineering, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, 510006, People's Republic of China
| | - Jingjing Zhao
- Department of Pharmaceutical Engineering, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, 510006, People's Republic of China.
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2
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Wang J, Wang X, Luo H, Xie Y, Cao H, Mao L, Liu T, Yue Y, Qian H. Extracellular vesicles in Helicobacter pylori-mediated diseases: mechanisms and therapeutic potential. Cell Commun Signal 2025; 23:79. [PMID: 39934861 DOI: 10.1186/s12964-025-02074-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Accepted: 01/29/2025] [Indexed: 02/13/2025] Open
Abstract
Extracellular vesicles (EVs) are relevant elements for cell-to-cell communication and are considered crucial in host-pathogen interactions by transferring molecules between the pathogen and the host during infections. These structures participate in various physiological and pathological processes and are considered promising candidates as disease markers, therapeutic reagents, and drug carriers. Both H. pylori and the host epithelial cells infected by H. pylori secrete EVs, which contribute to inflammation and the development of disease phenotypes. However, many aspects of the cellular and molecular biology of EV functions remain incompletely understood due to methodological challenges in studying these small structures. This review also highlights the roles of EVs derived from H. pylori-infected cells in the pathogenesis of gastric and extragastric diseases. Understanding the specific functions of these EVs during H. pylori infections, whether are advantageous to the host or the pathogen, may help the development new therapeutic approaches to prevent disease.
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Affiliation(s)
- Jianjun Wang
- Department of Clinical Laboratory, Kunshan Hospital Affiliated to Jiangsu University, Suzhou, Jiangsu, 215300, China
| | - Xiuping Wang
- Department of Clinical Laboratory, Kunshan Hospital Affiliated to Jiangsu University, Suzhou, Jiangsu, 215300, China
| | - Hao Luo
- Department of Clinical Laboratory, The Second People's Hospital of Kunshan, Suzhou, Jiangsu, 215300, China
| | - Yiping Xie
- Department of Clinical Laboratory, Kunshan Hospital Affiliated to Jiangsu University, Suzhou, Jiangsu, 215300, China
| | - Hui Cao
- Department of Food and Nutrition Safety, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu, 210003, China
| | - Lingxiang Mao
- Department of Clinical Laboratory, Kunshan Hospital Affiliated to Jiangsu University, Suzhou, Jiangsu, 215300, China
| | - Tingting Liu
- Science and Technology Talent Department, Kunshan Hospital Affiliated to Jiangsu University, Suzhou, Jiangsu, 215300, China
| | - Yushan Yue
- Department of Rehabilitative Medicine, Kunshan Hospital Affiliated to Jiangsu University, Suzhou, Jiangsu, 215300, China
| | - Hui Qian
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, Department of Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhengjiang, Jiangsu, 212013, China.
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3
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Wang X, Wang J, Mao L, Yao Y. Helicobacter pylori outer membrane vesicles and infected cell exosomes: new players in host immune modulation and pathogenesis. Front Immunol 2024; 15:1512935. [PMID: 39726601 PMCID: PMC11670821 DOI: 10.3389/fimmu.2024.1512935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Accepted: 11/27/2024] [Indexed: 12/28/2024] Open
Abstract
Outer membrane vesicles (OMVs) and exosomes are essential mediators of host-pathogen interactions. Elucidating their mechanisms of action offers valuable insights into diagnosing and treating infectious diseases and cancers. However, the specific interactions of Helicobacter pylori (H. pylori) with host cells via OMVs and exosomes in modulating host immune responses have not been thoroughly investigated. This review explores how these vesicles elicit inflammatory and immunosuppressive responses in the host environment, facilitate pathogen invasion of host cells, and enable evasion of host defenses, thereby contributing to the progression of gastric diseases and extra-gastric diseases disseminated through the bloodstream. Furthermore, the review discusses the challenges and future directions for investigating OMVs and exosomes, underscoring their potential as therapeutic targets in H. pylori-associated diseases.
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Affiliation(s)
- Xiuping Wang
- Department of Clinical Laboratory, The First People’s Hospital of
Kunshan, Kunshan, Jiangsu, China
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4
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Xiang S, Khan A, Yao Q, Wang D. Recent advances in bacterial outer membrane vesicles: Effects on the immune system, mechanisms and their usage for tumor treatment. J Pharm Anal 2024; 14:101049. [PMID: 39840399 PMCID: PMC11750273 DOI: 10.1016/j.jpha.2024.101049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2024] [Revised: 06/27/2024] [Accepted: 07/19/2024] [Indexed: 01/23/2025] Open
Abstract
Tumor treatment remains a significant medical challenge, with many traditional therapies causing notable side effects. Recent research has led to the development of immunotherapy, which offers numerous advantages. Bacteria inherently possess motility, allowing them to preferentially colonize tumors and modulate the tumor immune microenvironment, thus influencing the efficacy of immunotherapy. Bacterial outer membrane vesicles (OMVs) secreted by gram-negative bacteria are nanoscale lipid bilayer structures rich in bacterial antigens, pathogen-associated molecular patterns (PAMPs), various proteins, and vesicle structures. These features allow OMVs to stimulate immune system activation, generate immune responses, and serve as efficient drug delivery vehicles. This dual capability enhances the effectiveness of immunotherapy combined with chemotherapy or phototherapy, thereby improving anticancer drug efficacy. Current research has concentrated on engineering OMVs to enhance production yield, minimize cytotoxicity, and improve the safety and efficacy of treatments. Consequently, OMVs hold great promise for applications in tumor immunotherapy, tumor vaccine development, and drug delivery. This article provides an overview of the structural composition and immune mechanisms of OMVs, details various OMVs modification strategies, and reviews the progress in using OMVs for tumor treatment and their anti-tumor mechanisms. Additionally, it discusses the challenges faced in translating OMV-based anti-tumor therapies into clinical practice, aiming to provide a comprehensive understanding of OMVs' potential for in-depth research and clinical application.
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Affiliation(s)
- Shuo Xiang
- Center for AIE Research, Shenzhen Key Laboratory of Polymer Science and Technology, Guangdong Research Center for Interfacial Engineering of Functional Materials, College of Materials Science and Engineering, Shenzhen University, Shenzhen, Guangdong, 518060, China
- College of Advanced Materials Engineering, Jiaxing Nanhu University, 572 Yuexiu Road, Jiaxing, Zhejiang, 314001, China
| | - Arshad Khan
- Nanomedicine Department, King Abdullah International Medical Research Center (KAIMRC), King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Riyadh, 11426, Saudi Arabia
| | - Qiufang Yao
- College of Advanced Materials Engineering, Jiaxing Nanhu University, 572 Yuexiu Road, Jiaxing, Zhejiang, 314001, China
| | - Dong Wang
- Center for AIE Research, Shenzhen Key Laboratory of Polymer Science and Technology, Guangdong Research Center for Interfacial Engineering of Functional Materials, College of Materials Science and Engineering, Shenzhen University, Shenzhen, Guangdong, 518060, China
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5
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Easter QT, Alvarado-Martinez Z, Kunz M, Matuck BF, Rupp BT, Weaver T, Ren Z, Tata A, Caballero-Perez J, Oscarson N, Hasuike A, Ghodke AN, Kimple AJ, Tata PR, Randell SH, Koo H, Ko KI, Byrd KM. Polybacterial Intracellular Macromolecules Shape Single-Cell Epikine Profiles in Upper Airway Mucosa. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.10.08.617279. [PMID: 39416216 PMCID: PMC11482982 DOI: 10.1101/2024.10.08.617279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 10/19/2024]
Abstract
The upper airway, particularly the nasal and oral mucosal epithelium, serves as a primary barrier for microbial interactions throughout life. Specialized niches like the anterior nares and the tooth are especially susceptible to dysbiosis and chronic inflammatory diseases. To investigate host-microbial interactions in mucosal epithelial cell types, we reanalyzed our single-cell RNA sequencing atlas of human oral mucosa, identifying polybacterial signatures (20% Gram-positive, 80% Gram-negative) within both epithelial- and stromal-resident cells. This analysis revealed unique responses of bacterial-associated epithelia when compared to two inflammatory disease states of mucosa. Single-cell RNA sequencing, in situ hybridization, and immunohistochemistry detected numerous persistent macromolecules from Gram-positive and Gram-negative bacteria within human oral keratinocytes (HOKs), including bacterial rRNA, mRNA and glycolipids. Epithelial cells with higher concentrations of 16S rRNA and glycolipids exhibited enhanced receptor-ligand signaling in vivo. HOKs with a spectrum of polybacterial intracellular macromolecular (PIM) concentrations were challenged with purified exogenous lipopolysaccharide, resulting in the synergistic upregulation of select innate (CXCL8, TNFSF15) and adaptive (CXCL17, CCL28) epikines. Notably, endogenous lipoteichoic acid, rather than lipopolysaccharide, directly correlated with epikine expression in vitro and in vivo. Application of the Drug2Cell algorithm to health and inflammatory disease data suggested altered drug efficacy predictions based on PIM detection. Our findings demonstrate that PIMs persist within mucosal epithelial cells at variable concentrations, linearly driving single-cell effector cytokine expression and influencing drug responses, underscoring the importance of understanding host-microbe interactions and the implications of PIMs on cell behavior in health and disease at single-cell resolution.
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Affiliation(s)
- Quinn T Easter
- Lab of Oral & Craniofacial Innovation (LOCI), ADA Science & Research Institute, Gaithersburg, MD, USA
| | - Zabdiel Alvarado-Martinez
- Lab of Oral & Craniofacial Innovation (LOCI), ADA Science & Research Institute, Gaithersburg, MD, USA
| | - Meik Kunz
- The Bioinformatics CRO, Orlando, FL, USA
| | - Bruno Fernandes Matuck
- Lab of Oral & Craniofacial Innovation (LOCI), ADA Science & Research Institute, Gaithersburg, MD, USA
| | - Brittany T Rupp
- Lab of Oral & Craniofacial Innovation (LOCI), ADA Science & Research Institute, Gaithersburg, MD, USA
| | - Theresa Weaver
- Lab of Oral & Craniofacial Innovation (LOCI), ADA Science & Research Institute, Gaithersburg, MD, USA
| | - Zhi Ren
- Biofilm Research Laboratories, Center for Innovation & Precision Dentistry, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Aleksandra Tata
- Department of Cell Biology, Duke University School of Medicine, Durham, NC, USA
| | | | - Nick Oscarson
- Lab of Oral & Craniofacial Innovation (LOCI), ADA Science & Research Institute, Gaithersburg, MD, USA
| | - Akira Hasuike
- Lab of Oral & Craniofacial Innovation (LOCI), ADA Science & Research Institute, Gaithersburg, MD, USA
- Department of Periodontology, Nihon University School of Dentistry, Tokyo, JP
| | - Ameer N Ghodke
- Department of Otolaryngology-Head and Neck Surgery, University of North Carolina School of Medicine, Chapel Hill, NC, USA
| | - Adam J Kimple
- Department of Otolaryngology-Head and Neck Surgery, University of North Carolina School of Medicine, Chapel Hill, NC, USA
- Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Purushothama R Tata
- Department of Cell Biology, Duke University School of Medicine, Durham, NC, USA
| | - Scott H Randell
- Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Hyun Koo
- Biofilm Research Laboratories, Center for Innovation & Precision Dentistry, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Kang I Ko
- Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Kevin M Byrd
- Lab of Oral & Craniofacial Innovation (LOCI), ADA Science & Research Institute, Gaithersburg, MD, USA
- UNC Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
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Savitri CMA, Fauzia KA, Alfaray RI, Aftab H, Syam AF, Lubis M, Yamaoka Y, Miftahussurur M. Opportunities for Helicobacter pylori Eradication beyond Conventional Antibiotics. Microorganisms 2024; 12:1986. [PMID: 39458296 PMCID: PMC11509656 DOI: 10.3390/microorganisms12101986] [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: 07/31/2024] [Revised: 09/14/2024] [Accepted: 09/19/2024] [Indexed: 10/28/2024] Open
Abstract
Helicobacter pylori (H. pylori) is a bacterium known to be associated with a significant risk of gastric cancer in addition to chronic gastritis, peptic ulcer, and MALT lymphoma. Although only a small percentage of patients infected with H. pylori develop gastric cancer, Gastric cancer causes more than 750,000 deaths worldwide, with 90% of cases being caused by H. pylori. The eradication of this bacterium rests on multiple drug regimens as guided by various consensus. However, the efficacy of empirical therapy is decreasing due to antimicrobial resistance. In addition, biofilm formation complicates eradication. As the search for new antibiotics lags behind the bacterium's ability to mutate, studies have been directed toward finding new anti-H. pylori agents while also optimizing current drug functions. Targeting biofilm, repurposing outer membrane vesicles that were initially a virulence factor of the bacteria, phage therapy, probiotics, and the construction of nanoparticles might be able to complement or even be alternatives for H. pylori treatment. This review aims to present reports on various compounds, either new or combined with current antibiotics, and their pathways to counteract H. pylori resistance.
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Affiliation(s)
- Camilia Metadea Aji Savitri
- Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu 879-5593, Oita, Japan; (C.M.A.S.); (R.I.A.)
- Helicobacter Pylori and Microbiota Study Group, Institute of Tropical Disease, Universitas Airlangga, Surabaya 60286, Indonesia;
| | - Kartika Afrida Fauzia
- Helicobacter Pylori and Microbiota Study Group, Institute of Tropical Disease, Universitas Airlangga, Surabaya 60286, Indonesia;
- Research Centre for Preclinical and Clinical Medicine, National Research and Innovation Agency, Cibinong Science Center, Bogor 16915, Indonesia
| | - Ricky Indra Alfaray
- Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu 879-5593, Oita, Japan; (C.M.A.S.); (R.I.A.)
- Helicobacter Pylori and Microbiota Study Group, Institute of Tropical Disease, Universitas Airlangga, Surabaya 60286, Indonesia;
| | - Hafeza Aftab
- Department of Gastroenterology, Dhaka Medical College and Hospital, Dhaka 1000, Bangladesh;
| | - Ari Fahrial Syam
- Division of Gastroenterology-Hepatology, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia;
| | - Masrul Lubis
- Division of Gastroenterology-Hepatology, Department of Internal Medicine, Faculty of Medicine, Universitas Sumatera Utara, Medan 20155, Indonesia;
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu 879-5593, Oita, Japan; (C.M.A.S.); (R.I.A.)
- Helicobacter Pylori and Microbiota Study Group, Institute of Tropical Disease, Universitas Airlangga, Surabaya 60286, Indonesia;
- Department of Medicine, Gastroenterology and Hepatology Section, Baylor College of Medicine, Houston, TX 77030, USA
- Division of Genome-Wide Microbiology, Research Center for Global and Local Infectious Diseases (RCGLID), Oita University, Yufu 879-5593, Oita, Japan
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine—Dr. Soetomo Teaching Hospital, Universitas Airlangga, Surabaya 60286, Indonesia
| | - Muhammad Miftahussurur
- Helicobacter Pylori and Microbiota Study Group, Institute of Tropical Disease, Universitas Airlangga, Surabaya 60286, Indonesia;
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine—Dr. Soetomo Teaching Hospital, Universitas Airlangga, Surabaya 60286, Indonesia
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Margutti P, D’Ambrosio A, Zamboni S. Microbiota-Derived Extracellular Vesicle as Emerging Actors in Host Interactions. Int J Mol Sci 2024; 25:8722. [PMID: 39201409 PMCID: PMC11354844 DOI: 10.3390/ijms25168722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 07/26/2024] [Accepted: 08/01/2024] [Indexed: 09/02/2024] Open
Abstract
The human microbiota is an intricate micro-ecosystem comprising a diverse range of dynamic microbial populations mainly consisting of bacteria, whose interactions with hosts strongly affect several physiological and pathological processes. The gut microbiota is being increasingly recognized as a critical player in maintaining homeostasis, contributing to the main functions of the intestine and distal organs such as the brain. However, gut dysbiosis, characterized by composition and function alterations of microbiota with intestinal barrier dysfunction has been linked to the development and progression of several pathologies, including intestinal inflammatory diseases, systemic autoimmune diseases, such as rheumatic arthritis, and neurodegenerative diseases, such as Alzheimer's disease. Moreover, oral microbiota research has gained significant interest in recent years due to its potential impact on overall health. Emerging evidence on the role of microbiota-host interactions in health and disease has triggered a marked interest on the functional role of bacterial extracellular vesicles (BEVs) as mediators of inter-kingdom communication. Accumulating evidence reveals that BEVs mediate host interactions by transporting and delivering into host cells effector molecules that modulate host signaling pathways and cell processes, influencing health and disease. This review discusses the critical role of BEVs from the gut, lung, skin and oral cavity in the epithelium, immune system, and CNS interactions.
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Affiliation(s)
- Paola Margutti
- Department of Neurosciences, Istituto Superiore di Sanità, 00161 Rome, Italy; (A.D.); (S.Z.)
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Lin Y, Liu K, Lu F, Zhai C, Cheng F. Programmed cell death in Helicobacter pylori infection and related gastric cancer. Front Cell Infect Microbiol 2024; 14:1416819. [PMID: 39145306 PMCID: PMC11322058 DOI: 10.3389/fcimb.2024.1416819] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2024] [Accepted: 07/08/2024] [Indexed: 08/16/2024] Open
Abstract
Programmed cell death (PCD) plays a crucial role in maintaining the normal structure and function of the digestive tract in the body. Infection with Helicobacter pylori (H. pylori) is an important factor leading to gastric damage, promoting the Correa cascade and accelerating the transition from gastritis to gastric cancer. Recent research has shown that several PCD signaling pathways are abnormally activated during H. pylori infection, and the dysfunction of PCD is thought to contribute to the development of gastric cancer and interfere with treatment. With the deepening of studies on H. pylori infection in terms of PCD, exploring the interaction mechanisms between H. pylori and the body in different PCD pathways may become an important research direction for the future treatment of H. pylori infection and H. pylori-related gastric cancer. In addition, biologically active compounds that can inhibit or induce PCD may serve as key elements for the treatment of this disease. In this review, we briefly describe the process of PCD, discuss the interaction between different PCD signaling pathways and the mechanisms of H. pylori infection or H. pylori-related gastric cancer, and summarize the active molecules that may play a therapeutic role in each PCD pathway during this process, with the expectation of providing a more comprehensive understanding of the role of PCD in H. pylori infection.
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Affiliation(s)
- Yukun Lin
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Kunjing Liu
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Fang Lu
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Changming Zhai
- Department of Rheumatism, Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, China
| | - Fafeng Cheng
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
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Li J, Liao T, Chua EG, Zhang M, Shen Y, Song X, Marshall BJ, Benghezal M, Tang H, Li H. Helicobacter pylori Outer Membrane Vesicles: Biogenesis, Composition, and Biological Functions. Int J Biol Sci 2024; 20:4029-4043. [PMID: 39113715 PMCID: PMC11302881 DOI: 10.7150/ijbs.94156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Accepted: 07/06/2024] [Indexed: 08/10/2024] Open
Abstract
Helicobacter pylori has been recognized not only as a causative agent of a spectrum of gastroduodenal diseases including chronic gastritis, peptic ulcer, mucosa-associated lymphoid tissue lymphoma, and gastric cancer, but also as the culprit in several extra-gastric diseases. However, the association of H. pylori infection with extra-gastric diseases remains elusive, prompting a reevaluation of the role of H. pylori-derived outer membrane vesicles (OMVs). Like other gram-negative bacteria, H. pylori constitutively sheds biologically active OMVs for long-distance delivery of bacterial virulence factors in a concentrated and protected form, averting the need of direct bacterial contact with distant host cells to induce extra-gastric diseases associated with this gastric pathogen. Additionally, H. pylori-derived OMVs contribute to bacterial survival and chronic gastric pathogenesis. Moreover, the immunogenic activity, non-replicable nature, and anti-bacterial adhesion effect of H. pylori OMVs make them a desirable vaccine candidate against infection. The immunogenic potency and safety concerns of the OMV contents are challenges in the development of H. pylori OMV-based vaccines. In this review, we discuss recent advances regarding H. pylori OMVs, focusing on new insights into their biogenesis mechanisms and biological functions.
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Affiliation(s)
- Jiao Li
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Infectious and Liver Diseases, Institute of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, China
| | | | - Eng Guan Chua
- Helicobacter Research Laboratory, The Marshall Centre for Infectious Disease Research and Training, University of Western Australia, Nedlands WA 6009, Australia
| | - Mingming Zhang
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Infectious and Liver Diseases, Institute of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Yalin Shen
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Infectious and Liver Diseases, Institute of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Xiaona Song
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Infectious and Liver Diseases, Institute of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Barry J. Marshall
- Helicobacter Research Laboratory, The Marshall Centre for Infectious Disease Research and Training, University of Western Australia, Nedlands WA 6009, Australia
| | - Mohammed Benghezal
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Infectious and Liver Diseases, Institute of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Hong Tang
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Infectious and Liver Diseases, Institute of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Hong Li
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Infectious and Liver Diseases, Institute of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, China
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10
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Liu C, Yazdani N, Moran CS, Salomon C, Seneviratne CJ, Ivanovski S, Han P. Unveiling clinical applications of bacterial extracellular vesicles as natural nanomaterials in disease diagnosis and therapeutics. Acta Biomater 2024; 180:18-45. [PMID: 38641182 DOI: 10.1016/j.actbio.2024.04.022] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Revised: 03/03/2024] [Accepted: 04/11/2024] [Indexed: 04/21/2024]
Abstract
Bacterial extracellular vesicles (BEVs) are naturally occurring bioactive membrane-bound nanoparticles released by both gram-negative and gram-positive bacterial species, exhibiting a multifaceted role in mediating host-microbe interactions across various physiological conditions. Increasing evidence supports BEVs as essential mediators of cell-to-cell communicaiton, influencing bacterial pathogenicity, disease mechanisms, and modulating the host immune response. However, the extent to which these BEV-mediated actions can be leveraged to predict disease onset, guide treatment strategies, and determine clinical outcomes remains uncertain, particularly in terms of their clinical translation potentials. This review briefly describes BEV biogenesis and their internalisation by recipient cells and summarises methods for isolation and characterization, essential for understanding their composition and cargo. Further, it discusses the potential of biofluid-associated BEVs as biomarkers for various diseases, spanning both cancer and non-cancerous conditions. Following this, we outline the ongoing human clinical trials of using BEVs for vaccine development. In addition to disease diagnostics, this review explores the emerging research of using natural or engineered BEVs as smart nanomaterials for applications in anti-cancer therapy and bone regeneration. This discussion extends to key factors for unlocking the clinical potential of BEVs, such as standardization of BEV isolation and characterisation, as well as other hurdles in translating these findings to the clinical setting. We propose that addressing these hurdles through collaborative research efforts and well-designed clinical trials holds the key to fully harnessing the clinical potential of BEVs. As this field advances, this review suggests that BEV-based nanomedicine has the potential to revolutionize disease management, paving the way for innovative diagnosis, therapeutics, and personalized medicine approaches. STATEMENT OF SIGNIFICANCE: Extracellular vesicles (EVs) from both host cells and bacteria serve as multifunctional biomaterials and are emerging in the fields of biomedicine, bioengineering, and biomaterials. However, the majority of current studies focus on host-derived EVs, leaving a gap in comprehensive research on bacteria-derived EVs (BEVs). Although BEVs offer an attractive option as nanomaterials for drug delivery systems, their unique nanostructure and easy-to-modify functions make them a potential method for disease diagnosis and treatment as well as vaccine development. Our work among the pioneering studies investigating the potential of BEVs as natural nanobiomaterials plays a crucial role in both understanding the development of diseases and therapeutic interventions.
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Affiliation(s)
- Chun Liu
- The University of Queensland, School of Dentistry, Centre for Oralfacial Regeneration, Rehabilitation and Reconstruction (COR3), Epigenetics Nanodiagnostic and Therapeutic Group, Brisbane, QLD 4006, Australia
| | - Negar Yazdani
- The University of Queensland, School of Dentistry, Centre for Oralfacial Regeneration, Rehabilitation and Reconstruction (COR3), Epigenetics Nanodiagnostic and Therapeutic Group, Brisbane, QLD 4006, Australia
| | - Corey S Moran
- The University of Queensland, School of Dentistry, Centre for Oralfacial Regeneration, Rehabilitation and Reconstruction (COR3), Epigenetics Nanodiagnostic and Therapeutic Group, Brisbane, QLD 4006, Australia
| | - Carlos Salomon
- Translational Extracellular Vesicles in Obstetrics and Gynae-Oncology Group, The University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, Faculty of Medicine, The University of Queensland, Brisbane, QLD, 4029 Australia
| | - Chaminda Jayampath Seneviratne
- The University of Queensland, School of Dentistry, Centre for Oralfacial Regeneration, Rehabilitation and Reconstruction (COR3), Epigenetics Nanodiagnostic and Therapeutic Group, Brisbane, QLD 4006, Australia
| | - Sašo Ivanovski
- The University of Queensland, School of Dentistry, Centre for Oralfacial Regeneration, Rehabilitation and Reconstruction (COR3), Epigenetics Nanodiagnostic and Therapeutic Group, Brisbane, QLD 4006, Australia.
| | - Pingping Han
- The University of Queensland, School of Dentistry, Centre for Oralfacial Regeneration, Rehabilitation and Reconstruction (COR3), Epigenetics Nanodiagnostic and Therapeutic Group, Brisbane, QLD 4006, Australia.
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11
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Jarzab M, Skorko-Glonek J. There Are No Insurmountable Barriers: Passage of the Helicobacter pylori VacA Toxin from Bacterial Cytoplasm to Eukaryotic Cell Organelle. MEMBRANES 2023; 14:11. [PMID: 38248700 PMCID: PMC10821523 DOI: 10.3390/membranes14010011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 12/20/2023] [Accepted: 12/23/2023] [Indexed: 01/23/2024]
Abstract
The Gram-negative bacterium Helicobacter pylori is a very successful pathogen, one of the most commonly identified causes of bacterial infections in humans worldwide. H. pylori produces several virulence factors that contribute to its persistence in the hostile host habitat and to its pathogenicity. The most extensively studied are cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA). VacA is present in almost all H. pylori strains. As a secreted multifunctional toxin, it assists bacterial colonization, survival, and proliferation during long-lasting infections. To exert its effect on gastric epithelium and other cell types, VacA undergoes several modifications and crosses multiple membrane barriers. Once inside the gastric epithelial cell, VacA disrupts many cellular-signaling pathways and processes, leading mainly to changes in the efflux of various ions, the depolarization of membrane potential, and perturbations in endocytic trafficking and mitochondrial function. The most notable effect of VacA is the formation of vacuole-like structures, which may lead to apoptosis. This review focuses on the processes involved in VacA secretion, processing, and entry into host cells, with a particular emphasis on the interaction of the mature toxin with host membranes and the formation of transmembrane pores.
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Affiliation(s)
| | - Joanna Skorko-Glonek
- Department of General and Medical Biochemistry, Faculty of Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, Poland;
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12
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Meng R, Zeng M, Ji Y, Huang X, Xu M. The potential role of gut microbiota outer membrane vesicles in colorectal cancer. Front Microbiol 2023; 14:1270158. [PMID: 38029123 PMCID: PMC10661380 DOI: 10.3389/fmicb.2023.1270158] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Accepted: 10/02/2023] [Indexed: 12/01/2023] Open
Abstract
Colorectal cancer (CRC) is a common malignant digestive tract tumor in colorectal regions. Considerable evidence now shows that the gut microbiota have essential roles in CRC occurrence and development. Most Gram-negative bacteria release outer membrane vesicles (OMVs) via outer membrane blistering, which contain specific cargoes which interact with host cells via intercellular communications, host immune regulation, and gut microbiota homeostasis. Studies have also shown that OMVs selectively cluster near tumor cells, thus cancer treatment strategies based on OMVs have attracted considerable research attention. However, little is known about the possible impact of gut microbiota OMVs in CRC pathophysiology. Therefore, in this review, we summarize the research progress on molecular composition and function of OMV, and review the microbial dysbiosis in CRC. We then focus on the potential role of gut microbiota OMVs in CRC. Finally, we examine the clinical potential of OMVs in CRC treatment, and their main advantages and challenges in tumor therapy.
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Affiliation(s)
- Ran Meng
- Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
- Department of Biochemistry and Molecular Biology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Minmin Zeng
- Department of Biochemistry and Molecular Biology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Ying Ji
- Department of Biochemistry and Molecular Biology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Xinxiang Huang
- Department of Biochemistry and Molecular Biology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Min Xu
- Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
- Institute of Digestive Diseases, Jiangsu University, Zhenjiang, Jiangsu, China
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13
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Benešová I, Křížová Ľ, Kverka M. Microbiota as the unifying factor behind the hallmarks of cancer. J Cancer Res Clin Oncol 2023; 149:14429-14450. [PMID: 37555952 PMCID: PMC10590318 DOI: 10.1007/s00432-023-05244-6] [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: 05/05/2023] [Accepted: 08/01/2023] [Indexed: 08/10/2023]
Abstract
The human microbiota is a complex ecosystem that colonizes body surfaces and interacts with host organ systems, especially the immune system. Since the composition of this ecosystem depends on a variety of internal and external factors, each individual harbors a unique set of microbes. These differences in microbiota composition make individuals either more or less susceptible to various diseases, including cancer. Specific microbes are associated with cancer etiology and pathogenesis and several mechanisms of how they drive the typical hallmarks of cancer were recently identified. Although most microbes reside in the distal gut, they can influence cancer initiation and progression in distant tissues, as well as modulate the outcomes of established cancer therapies. Here, we describe the mechanisms by which microbes influence carcinogenesis and discuss their current and potential future applications in cancer diagnostics and management.
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Affiliation(s)
- Iva Benešová
- Laboratory of Cellular and Molecular Immunology, Institute of Microbiology v.v.i., Czech Academy of Sciences, Vídeňská 1083, 142 00, Prague 4-Krč, Czech Republic
| | - Ľudmila Křížová
- Department of Oncology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic
| | - Miloslav Kverka
- Laboratory of Cellular and Molecular Immunology, Institute of Microbiology v.v.i., Czech Academy of Sciences, Vídeňská 1083, 142 00, Prague 4-Krč, Czech Republic.
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14
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Gan Y, Zhao G, Wang Z, Zhang X, Wu MX, Lu M. Bacterial Membrane Vesicles: Physiological Roles, Infection Immunology, and Applications. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2023; 10:e2301357. [PMID: 37357142 PMCID: PMC10477901 DOI: 10.1002/advs.202301357] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 05/19/2023] [Indexed: 06/27/2023]
Abstract
Bacterial or fungal membrane vesicles, traditionally considered as microbial metabolic wastes, are secreted mainly from the outer membrane or cell membrane of microorganisms. However, recent studies have shown that these vesicles play essential roles in direct or indirect communications among microorganisms and between microorganisms and hosts. This review aims to provide an updated understanding of the physiological functions and emerging applications of bacterial membrane vesicles, with a focus on their biogenesis, mechanisms of adsorption and invasion into host cells, immune stimulatory effects, and roles in the much-concerned problem of bacterial resistance. Additionally, the potential applications of these vesicles as biomarkers, vaccine candidates, and drug delivery platforms are discussed.
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Affiliation(s)
- Yixiao Gan
- Department of Transfusion MedicineHuashan HospitalFudan UniversityShanghai200040P. R. China
| | - Gang Zhao
- Department of OrthopaedicsShanghai Key Laboratory for Prevention and Treatment of Bone and Joint DiseasesShanghai Institute of Traumatology and OrthopaedicsRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai200240P. R. China
| | - Zhicheng Wang
- Department of Transfusion MedicineHuashan HospitalFudan UniversityShanghai200040P. R. China
| | - Xingcai Zhang
- John A. Paulson School of Engineering and Applied SciencesHarvard UniversityCambridgeMA02138USA
| | - Mei X. Wu
- Wellman Center for PhotomedicineMassachusetts General HospitalDepartment of DermatologyHarvard Medical School, 50 Blossom StreetBostonMA02114USA
| | - Min Lu
- Department of OrthopaedicsShanghai Key Laboratory for Prevention and Treatment of Bone and Joint DiseasesShanghai Institute of Traumatology and OrthopaedicsRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai200240P. R. China
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15
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Xiao M, Li G, Yang H. Microbe-host interactions: structure and functions of Gram-negative bacterial membrane vesicles. Front Microbiol 2023; 14:1225513. [PMID: 37720140 PMCID: PMC10500606 DOI: 10.3389/fmicb.2023.1225513] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Accepted: 08/17/2023] [Indexed: 09/19/2023] Open
Abstract
Bacteria-host interaction is a common, relevant, and intriguing biological phenomena. The host reacts actively or passively to the bacteria themselves, their products, debris, and so on, through various defense systems containing the immune system, the bacteria communicate with the local or distal tissues of the host via their own surface antigens, secreted products, nucleic acids, etc., resulting in relationships of attack and defense, adaptation, symbiosis, and even collaboration. The significance of bacterial membrane vesicles (MVs) as a powerful vehicle for the crosstalk mechanism between the two is growing. In the recent decade, the emergence of MVs in microbial interactions and a variety of bacterial infections, with multiple adhesions to host tissues, cell invasion and evasion of host defense mechanisms, have brought MVs to the forefront of bacterial pathogenesis research. Whereas MVs are a complex combination of molecules not yet fully understood, research into its effects, targeting and pathogenic components will advance its understanding and utilization. This review will summarize structural, extraction and penetration information on several classes of MVs and emphasize the role of MVs in transport and immune response activation. Finally, the potential of MVs as a therapeutic method will be highlighted, as will future research prospects.
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Affiliation(s)
- Min Xiao
- Yunnan Key Laboratory of Stomatology, Kunming Medical University, Kunming, Yunnan, China
- Department of Dental Research, The Affiliated Stomatology Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Guiding Li
- Yunnan Key Laboratory of Stomatology, Kunming Medical University, Kunming, Yunnan, China
- Department of Dental Research, The Affiliated Stomatology Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Hefeng Yang
- Yunnan Key Laboratory of Stomatology, Kunming Medical University, Kunming, Yunnan, China
- Department of Dental Research, The Affiliated Stomatology Hospital of Kunming Medical University, Kunming, Yunnan, China
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16
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Chen S, Lei Q, Zou X, Ma D. The role and mechanisms of gram-negative bacterial outer membrane vesicles in inflammatory diseases. Front Immunol 2023; 14:1157813. [PMID: 37398647 PMCID: PMC10313905 DOI: 10.3389/fimmu.2023.1157813] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Accepted: 06/05/2023] [Indexed: 07/04/2023] Open
Abstract
Outer membrane vesicles (OMVs) are spherical, bilayered, and nanosized membrane vesicles that are secreted from gram-negative bacteria. OMVs play a pivotal role in delivering lipopolysaccharide, proteins and other virulence factors to target cells. Multiple studies have found that OMVs participate in various inflammatory diseases, including periodontal disease, gastrointestinal inflammation, pulmonary inflammation and sepsis, by triggering pattern recognition receptors, activating inflammasomes and inducing mitochondrial dysfunction. OMVs also affect inflammation in distant organs or tissues via long-distance cargo transport in various diseases, including atherosclerosis and Alzheimer's disease. In this review, we primarily summarize the role of OMVs in inflammatory diseases, describe the mechanism through which OMVs participate in inflammatory signal cascades, and discuss the effects of OMVs on pathogenic processes in distant organs or tissues with the aim of providing novel insights into the role and mechanism of OMVs in inflammatory diseases and the prevention and treatment of OMV-mediated inflammatory diseases.
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17
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Thapa HB, Ebenberger SP, Schild S. The Two Faces of Bacterial Membrane Vesicles: Pathophysiological Roles and Therapeutic Opportunities. Antibiotics (Basel) 2023; 12:1045. [PMID: 37370364 PMCID: PMC10295235 DOI: 10.3390/antibiotics12061045] [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: 05/30/2023] [Revised: 06/07/2023] [Accepted: 06/12/2023] [Indexed: 06/29/2023] Open
Abstract
Bacterial membrane vesicles (MVs) are nanosized lipid particles secreted by lysis or blebbing mechanisms from Gram-negative and -positive bacteria. It is becoming increasingly evident that MVs can promote antimicrobial resistance but also provide versatile opportunities for therapeutic exploitation. As non-living facsimiles of parent bacteria, MVs can carry multiple bioactive molecules such as proteins, lipids, nucleic acids, and metabolites, which enable them to participate in intra- and interspecific communication. Although energetically costly, the release of MVs seems beneficial for bacterial fitness, especially for pathogens. In this review, we briefly discuss the current understanding of diverse MV biogenesis routes affecting MV cargo. We comprehensively highlight the physiological functions of MVs derived from human pathogens covering in vivo adaptation, colonization fitness, and effector delivery. Emphasis is given to recent findings suggesting a vicious cycle of MV biogenesis, pathophysiological function, and antibiotic therapy. We also summarize potential therapeutical applications, such as immunotherapy, vaccination, targeted delivery, and antimicrobial potency, including their experimental validation. This comparative overview identifies common and unique strategies for MV modification used along diverse applications. Thus, the review summarizes timely aspects of MV biology in a so far unprecedented combination ranging from beneficial function for bacterial pathogen survival to future medical applications.
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Affiliation(s)
- Himadri B. Thapa
- Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50, 8010 Graz, Austria
| | - Stephan P. Ebenberger
- Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50, 8010 Graz, Austria
| | - Stefan Schild
- Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50, 8010 Graz, Austria
- BioTechMed Graz, 8010 Graz, Austria
- Field of Excellence Biohealth, University of Graz, 8010 Graz, Austria
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18
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Luo R, Chang Y, Liang H, Zhang W, Song Y, Li G, Yang C. Interactions between extracellular vesicles and microbiome in human diseases: New therapeutic opportunities. IMETA 2023; 2:e86. [PMID: 38868436 PMCID: PMC10989913 DOI: 10.1002/imt2.86] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Revised: 12/21/2022] [Accepted: 01/14/2023] [Indexed: 06/14/2024]
Abstract
In recent decades, accumulating research on the interactions between microbiome homeostasis and host health has broadened new frontiers in delineating the molecular mechanisms of disease pathogenesis and developing novel therapeutic strategies. By transporting proteins, nucleic acids, lipids, and metabolites in their versatile bioactive molecules, extracellular vesicles (EVs), natural bioactive cell-secreted nanoparticles, may be key mediators of microbiota-host communications. In addition to their positive and negative roles in diverse physiological and pathological processes, there is considerable evidence to implicate EVs secreted by bacteria (bacterial EVs [BEVs]) in the onset and progression of various diseases, including gastrointestinal, respiratory, dermatological, neurological, and musculoskeletal diseases, as well as in cancer. Moreover, an increasing number of studies have explored BEV-based platforms to design novel biomedical diagnostic and therapeutic strategies. Hence, in this review, we highlight the recent advances in BEV biogenesis, composition, biofunctions, and their potential involvement in disease pathologies. Furthermore, we introduce the current and emerging clinical applications of BEVs in diagnostic analytics, vaccine design, and novel therapeutic development.
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Affiliation(s)
- Rongjin Luo
- Department of Orthopaedics, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
- Department of Spine Surgery, Honghui HospitalXi'an Jiaotong UniversityXi'anChina
| | - Yanmin Chang
- Department of Neurology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Huaizhen Liang
- Department of Orthopaedics, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Weifeng Zhang
- Department of Orthopaedics, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Yu Song
- Department of Orthopaedics, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Gaocai Li
- Department of Orthopaedics, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Cao Yang
- Department of Orthopaedics, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
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19
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Tian CM, Yang MF, Xu HM, Zhu MZ, Zhang Y, Yao J, Wang LS, Liang YJ, Li DF. Emerging role of bacterial outer membrane vesicle in gastrointestinal tract. Gut Pathog 2023; 15:20. [PMID: 37106359 PMCID: PMC10133921 DOI: 10.1186/s13099-023-00543-2] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Accepted: 03/30/2023] [Indexed: 04/29/2023] Open
Abstract
Bacteria form a highly complex ecosystem in the gastrointestinal (GI) tract. In recent years, mounting evidence has shown that bacteria can release nanoscale phospholipid bilayer particles that encapsulate nucleic acids, proteins, lipids, and other molecules. Extracellular vesicles (EVs) are secreted by microorganisms and can transport a variety of important factors, such as virulence factors, antibiotics, HGT, and defensive factors produced by host eukaryotic cells. In addition, these EVs are vital in facilitating communication between microbiota and the host. Therefore, bacterial EVs play a crucial role in maintaining the GI tract's health and proper functioning. In this review, we outlined the structure and composition of bacterial EVs. Additionally, we highlighted the critical role that bacterial EVs play in immune regulation and in maintaining the balance of the gut microbiota. To further elucidate progress in the field of intestinal research and to provide a reference for future EV studies, we also discussed the clinical and pharmacological potential of bacterial EVs, as well as the necessary efforts required to understand the mechanisms of interaction between bacterial EVs and gut pathogenesis.
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Affiliation(s)
- Cheng-Mei Tian
- Department of Emergency, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, Guangdong, China
| | - Mei-Feng Yang
- Department of Hematology, Yantian District People's Hospital, Shenzhen, Guangdong, China
| | - Hao-Ming Xu
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Min-Zheng Zhu
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Yuan Zhang
- Department of Medical Administration, Huizhou Institute of Occupational Diseases Control and Prevention, Huizhou, Guangdong, China
| | - Jun Yao
- Department of Gastroenterology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; the First Affiliated Hospital, Southern University of Science and Technology), No.1017, Dongmen North Road, Luohu District, Shenzhen, 518020, People's Republic of China.
| | - Li-Sheng Wang
- Department of Gastroenterology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; the First Affiliated Hospital, Southern University of Science and Technology), No.1017, Dongmen North Road, Luohu District, Shenzhen, 518020, People's Republic of China.
| | - Yu-Jie Liang
- Department of Child and Adolescent Psychiatry, Shenzhen Kangning Hospital, No.1080, Cuizu Road, Luohu District, Shenzhen, 518020, People's Republic of China.
| | - De-Feng Li
- Department of Gastroenterology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; the First Affiliated Hospital, Southern University of Science and Technology), No.1017, Dongmen North Road, Luohu District, Shenzhen, 518020, People's Republic of China.
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20
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Saberi S, Esmaeili M, Saghiri R, Shekari F, Mohammadi M. Assessment of the mixed origin of the gastric epithelial extracellular vesicles in acellular transfer of Helicobacter pylori toxins and a systematic review. Microb Pathog 2023; 177:106024. [PMID: 36758823 DOI: 10.1016/j.micpath.2023.106024] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Revised: 02/01/2023] [Accepted: 02/03/2023] [Indexed: 02/10/2023]
Abstract
BACKGROUND H. pylori are generally considered as extracellular organisms, with exclusive colonization of the gastric milieu. Yet, several extra gastric manifestations are associated with this infection. The aim of the present study was to investigate the feasibility of toxin transfer by extracellular vesicles, from bacterial and epithelial origins. METHODS Tox-positive H. pylori and its two cagA and vacA mutant strains were used to produce bacterial vesicles (BVs) and to infect AGS cells. The produced BVs and the infected cell vesicles (ICVs) were collected by ultracentrifugation and evaluated by western blotting, DLS and electron microscopy. These two sets of vesicles were applied to a second set of recipient AGS cells, in which the acellular transfer of toxins, IL-8 production and downstream morphologic changes were assessed, by western blotting, ELISA and light microscopy, respectively. RESULTS The BVs were positive for H. pylori membrane markers (BabA and UreB), VacA and CagA toxins, except for from the corresponding mutant strains. The ICVs were larger in size and positive for bacterial markers, as well as epithelial markers of CD9, LGR5, but negative for nuclear (Ki76) or cytoplasmic (β-actin) markers. Bacteria-independent transfer of CagA and VacA into the recipient cells occurred upon treatment of cells with BVs and ICVs, followed by cellular vacuolation and elongation. IL-8 production was induced in recipient AGS cells, treated with BVs (1279.4 ± 19.79 pg/106 cells), early (8 h, 1171.4 ± 11.31 pg/106 cells) and late (48 h, 965.4 ± 36.77 pg/106 cells) ICVs (P < 0.0001). CONCLUSION Our data indicates that ICVs, with mixed bacterial and epithelial constituents, similar to BVs, are capable of transferring bacterial toxins into the recipient cells, inducing IL-8 production and subsequent morphologic changes, in an acellular manner.
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Affiliation(s)
- Samaneh Saberi
- HPGC Research Group, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
| | - Maryam Esmaeili
- HPGC Research Group, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
| | - Reza Saghiri
- Department of Biochemistry, Pasteur Institute of Iran, Tehran, Iran
| | - Faezeh Shekari
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Advanced Therapy Medicinal Product Technology Development Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Marjan Mohammadi
- HPGC Research Group, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
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21
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Jalalifar S, Morovati Khamsi H, Hosseini-Fard SR, Karampoor S, Bajelan B, Irajian G, Mirzaei R. Emerging role of microbiota derived outer membrane vesicles to preventive, therapeutic and diagnostic proposes. Infect Agent Cancer 2023; 18:3. [PMID: 36658631 PMCID: PMC9850788 DOI: 10.1186/s13027-023-00480-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2022] [Accepted: 01/12/2023] [Indexed: 01/20/2023] Open
Abstract
The role of gut microbiota and its products in human health and disease is profoundly investigated. The communication between gut microbiota and the host involves a complicated network of signaling pathways via biologically active molecules generated by intestinal microbiota. Some of these molecules could be assembled within nanoparticles known as outer membrane vesicles (OMVs). Recent studies propose that OMVs play a critical role in shaping immune responses, including homeostasis and acute inflammatory responses. Moreover, these OMVs have an immense capacity to be applied in medical research, such as OMV-based vaccines and drug delivery. This review presents a comprehensive overview of emerging knowledge about biogenesis, the role, and application of these bacterial-derived OMVs, including OMV-based vaccines, OMV adjuvants characteristics, OMV vehicles (in conjugated vaccines), cancer immunotherapy, and drug carriers and delivery systems. Moreover, we also highlight the significance of the potential role of these OMVs in diagnosis and therapy.
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Affiliation(s)
- Saba Jalalifar
- Microbial Biotechnology Research Center, Iran University of Medical Sciences, Tehran, Iran
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Hassan Morovati Khamsi
- Department of Quality Control, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran
| | - Seyed Reza Hosseini-Fard
- Department of Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Sajad Karampoor
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Bahar Bajelan
- School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
| | - Gholamreza Irajian
- Microbial Biotechnology Research Center, Iran University of Medical Sciences, Tehran, Iran.
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
| | - Rasoul Mirzaei
- Venom and Biotherapeutics Molecules Lab, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
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22
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Abstract
This review focuses on nonlytic outer membrane vesicles (OMVs), a subtype of bacterial extracellular vesicles (BEVs) produced by Gram-negative organisms focusing on the mechanisms of their biogenesis, cargo, and function. Throughout, we highlight issues concerning the characterization of OMVs and distinguishing them from other types of BEVs. We also highlight the shortcomings of commonly used methodologies for the study of BEVs that impact the interpretation of their functionality and suggest solutions to standardize protocols for OMV studies.
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Affiliation(s)
| | - Simon R. Carding
- Quadram Institute Bioscience, Norwich, United Kingdom
- Norwich Medical School, University of East Anglia, Norwich, United Kingdom
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23
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Suri K, D'Souza A, Huang D, Bhavsar A, Amiji M. Bacterial extracellular vesicle applications in cancer immunotherapy. Bioact Mater 2022; 22:551-566. [PMID: 36382022 PMCID: PMC9637733 DOI: 10.1016/j.bioactmat.2022.10.024] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Revised: 10/10/2022] [Accepted: 10/22/2022] [Indexed: 12/03/2022] Open
Abstract
Cancer therapy is undergoing a paradigm shift toward immunotherapy focusing on various approaches to activate the host immune system. As research to identify appropriate immune cells and activate anti-tumor immunity continues to expand, scientists are looking at microbial sources given their inherent ability to elicit an immune response. Bacterial extracellular vesicles (BEVs) are actively studied to control systemic humoral and cellular immune responses instead of using whole microorganisms or other types of extracellular vesicles (EVs). BEVs also provide the opportunity as versatile drug delivery carriers. Unlike mammalian EVs, BEVs have already made it to the clinic with the meningococcal vaccine (Bexsero®). However, there are still many unanswered questions in the use of BEVs, especially for chronic systemically administered immunotherapies. In this review, we address the opportunities and challenges in the use of BEVs for cancer immunotherapy and provide an outlook towards development of BEV products that can ultimately translate to the clinic.
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Affiliation(s)
- Kanika Suri
- Department of Bioengineering, College of Engineering, Northeastern University, Boston, MA, 02115, USA
| | - Anisha D'Souza
- Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, MA, 02115, USA,Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, 20115, USA
| | - Di Huang
- Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, MA, 02115, USA,Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, 20115, USA
| | - Aashray Bhavsar
- Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, MA, 02115, USA
| | - Mansoor Amiji
- Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, MA, 02115, USA,Department of Chemical Engineering, College of Engineering, Northeastern University, Boston, MA, 02115, USA,Corresponding author. Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, MA, 02115, USA.
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Wang S, Guo J, Bai Y, Sun C, Wu Y, Liu Z, Liu X, Wang Y, Wang Z, Zhang Y, Hao H. Bacterial outer membrane vesicles as a candidate tumor vaccine platform. Front Immunol 2022; 13:987419. [PMID: 36159867 PMCID: PMC9505906 DOI: 10.3389/fimmu.2022.987419] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Accepted: 08/22/2022] [Indexed: 11/17/2022] Open
Abstract
Cancer represents a serious concern for human life and health. Due to drug resistance and the easy metastasis of tumors, there is urgent need to develop new cancer treatment methods beyond the traditional radiotherapy, chemotherapy, and surgery. Bacterial outer membrane vesicles (OMVs) are a type of double-membrane vesicle secreted by Gram-negative bacteria in the process of growth and life, and play extremely important roles in the survival and invasion of those bacteria. In particular, OMVs contain a large number of immunogenic components associated with their parent bacterium, which can be used as vaccines, adjuvants, and vectors to treat diseases, especially in presenting tumor antigens or targeted therapy with small-molecule drugs. Some OMV-based vaccines are already on the market and have demonstrated good therapeutic effect on the corresponding diseases. OMV-based vaccines for cancer are also being studied, and some are already in clinical trials. This paper reviews bacterial outer membrane vesicles, their interaction with host cells, and their applications in tumor vaccines.
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Affiliation(s)
- Shuming Wang
- State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, School of Life Science, Inner Mongolia University, Hohhot, China
| | - Jiayi Guo
- State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, School of Life Science, Inner Mongolia University, Hohhot, China
| | - Yang Bai
- State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, School of Life Science, Inner Mongolia University, Hohhot, China
| | - Cai Sun
- State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, School of Life Science, Inner Mongolia University, Hohhot, China
| | - Yanhao Wu
- State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, School of Life Science, Inner Mongolia University, Hohhot, China
| | - Zhe Liu
- State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, School of Life Science, Inner Mongolia University, Hohhot, China
| | - Xiaofei Liu
- State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, School of Life Science, Inner Mongolia University, Hohhot, China
| | - Yanfeng Wang
- State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, School of Life Science, Inner Mongolia University, Hohhot, China
| | - Zhigang Wang
- State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, School of Life Science, Inner Mongolia University, Hohhot, China
| | - Yongmin Zhang
- Inner Mongolia University Research Center for Glycochemistry of Characteristic Medicinal Resources, Department of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot, China
| | - Huifang Hao
- State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, School of Life Science, Inner Mongolia University, Hohhot, China
- Inner Mongolia University Research Center for Glycochemistry of Characteristic Medicinal Resources, Department of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot, China
- *Correspondence: Huifang Hao,
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25
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George E, Goswami A, Lodhiya T, Padwal P, Iyer S, Gauttam I, Sethi L, Jeyasankar S, Sharma PR, Dravid AA, Mukherjee R, Agarwal R. Immunomodulatory effect of mycobacterial outer membrane vesicles coated nanoparticles. BIOMATERIALS ADVANCES 2022; 139:213003. [PMID: 35882150 DOI: 10.1016/j.bioadv.2022.213003] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/06/2022] [Revised: 06/21/2022] [Accepted: 06/22/2022] [Indexed: 06/15/2023]
Abstract
Tuberculosis (TB) is one of the most widely prevalent infectious diseases that cause significant mortality. Bacillus Calmette-Guérin (BCG), the current TB vaccine used in clinics, shows variable efficacy and has safety concerns for immunocompromised patients. There is a need to develop new and more effective TB vaccines. Outer membrane vesicles (OMVs) are vesicles released by Mycobacteria that contain several lipids and membrane proteins and act as a good source of antigens to prime immune response. However, the use of OMVs as vaccines has been hampered by their heterogeneous size and low stability. Here we report that mycobacterial OMVs can be stabilized by coating over uniform-sized 50 nm gold nanoparticles. The OMV-coated gold nanoparticles (OMV-AuNP) show enhanced uptake and activation of macrophages and dendritic cells. Proteinase K and TLR inhibitor studies demonstrated that the enhanced activation was attributed to proteins present on OMVs and was mediated primarily by TLR2 and TLR4. Mass spectrometry analysis revealed several potential membrane proteins that were common in both free OMVs and OMV-AuNP. Such strategies may open up new avenues and the utilization of novel antigens for developing TB vaccines.
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Affiliation(s)
- Edna George
- Centre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore, India
| | - Avijit Goswami
- Centre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore, India
| | - Tejan Lodhiya
- Indian Institute of Science Education and Research, Tirupati, India
| | - Priyanka Padwal
- Centre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore, India
| | - Shalini Iyer
- Centre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore, India
| | - Iti Gauttam
- Centre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore, India
| | - Lakshay Sethi
- Centre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore, India
| | - Sharumathi Jeyasankar
- Centre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore, India
| | - Pallavi Raj Sharma
- Centre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore, India
| | - Ameya Atul Dravid
- Centre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore, India
| | - Raju Mukherjee
- Indian Institute of Science Education and Research, Tirupati, India
| | - Rachit Agarwal
- Centre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore, India.
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26
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Mat Rani NNI, Alzubaidi ZM, Butt AM, Mohammad Faizal NDF, Sekar M, Azhari H, Mohd Amin MCI. Outer membrane vesicles as biomimetic vaccine carriers against infections and cancers. WILEY INTERDISCIPLINARY REVIEWS. NANOMEDICINE AND NANOBIOTECHNOLOGY 2022; 14:e1784. [PMID: 35194964 DOI: 10.1002/wnan.1784] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Revised: 01/18/2022] [Accepted: 02/03/2022] [Indexed: 06/14/2023]
Abstract
In the last decade, nanoparticle-based therapeutic modalities have emerged as promising treatment options for cancer and infectious diseases. To improve prognosis, chemotherapeutic and antimicrobial drugs must be delivered selectively to the target sites. Researchers have increasingly focused their efforts on improving drug delivery, with a particular emphasis on cancer and infectious diseases. When drugs are administered systemically, they become diluted and can diffuse to all tissues but only until the immune system intervenes and quickly removes them from circulation. To enhance and prolong the systemic circulation of drugs, nanocarriers have been explored and used; however, nanocarriers have a major drawback in that they can trigger immune responses. Numerous nanocarriers for optimal drug delivery have been developed using innovative and effective biointerface technologies. Autologous cell-derived drug carriers, such as outer membrane vesicles (OMVs), have demonstrated improved bioavailability and reduced toxicity. Thus, this study investigates the use of biomimetic OMVs as biomimetic vaccine carriers against infections and cancers to improve our understanding in the field of nanotechnology. In addition, discussion on the advantages, disadvantages, and future prospects of OMVs will also be explored. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Biology-Inspired Nanomaterials > Protein and Virus-Based Structures.
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Affiliation(s)
- Nur Najihah Izzati Mat Rani
- Centre for Drug Delivery Technology, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur, Malaysia
- Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, Perak, Malaysia
| | - Zahraa M Alzubaidi
- Centre for Drug Delivery Technology, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur, Malaysia
| | - Adeel Masood Butt
- Institute of Pharmaceutical Sciences, University of Veterinary and Animal Sciences, Lahore, Pakistan
| | - Nur Dini Fatini Mohammad Faizal
- Centre for Drug Delivery Technology, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur, Malaysia
| | - Mahendran Sekar
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, Perak, Malaysia
| | - Hanisah Azhari
- Centre for Drug Delivery Technology, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur, Malaysia
| | - Mohd Cairul Iqbal Mohd Amin
- Centre for Drug Delivery Technology, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur, Malaysia
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27
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Zou C, Zhang Y, Liu H, Wu Y, Zhou X. Extracellular Vesicles: Recent Insights Into the Interaction Between Host and Pathogenic Bacteria. Front Immunol 2022; 13:840550. [PMID: 35693784 PMCID: PMC9174424 DOI: 10.3389/fimmu.2022.840550] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Accepted: 04/27/2022] [Indexed: 02/05/2023] Open
Abstract
Extracellular vesicles (EVs) are nanosized lipid particles released by virtually every living cell. EVs carry bioactive molecules, shuttle from cells to cells and transduce signals, regulating cell growth and metabolism. Pathogenic bacteria can cause serious infections via a wide range of strategies, and host immune systems also develop extremely complex adaptations to counteract bacterial infections. As notable carriers, EVs take part in the interaction between the host and bacteria in several approaches. For host cells, several strategies have been developed to resist bacteria via EVs, including expelling damaged membranes and bacteria, neutralizing toxins, triggering innate immune responses and provoking adaptive immune responses in nearly the whole body. For bacteria, EVs function as vehicles to deliver toxins and contribute to immune escape. Due to their crucial functions, EVs have great application potential in vaccines, diagnosis and treatments. In the present review, we highlight the most recent advances, application potential and remaining challenges in understanding EVs in the interaction between the host and bacteria.
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Affiliation(s)
- Chaoyu Zou
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China
- Department of Hematology and Hematology Research Laboratory, West China Hospital, Sichuan University, Chengdu, China
| | - Yige Zhang
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Huan Liu
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Yu Wu
- Department of Hematology and Hematology Research Laboratory, West China Hospital, Sichuan University, Chengdu, China
| | - Xikun Zhou
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China
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Qiang L, Hu J, Tian M, Li Y, Ren C, Deng Y, Jiang Y. Extracellular vesicles from helicobacter pylori-infected cells and helicobacter pylori outer membrane vesicles in atherosclerosis. Helicobacter 2022; 27:e12877. [PMID: 35099837 DOI: 10.1111/hel.12877] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 12/26/2021] [Accepted: 01/11/2022] [Indexed: 12/15/2022]
Abstract
BACKGROUND The role of H. pylori infection has been reported in various extragastric diseases, particularly, the correlation between H. pylori and atherosclerosis (AS) have received lots of attention. Some scholars demonstrated that the presence of H. pylori-specific DNA in the sclerotic plaques of atheromatous patients provides biological evidences, with indicating that H. pylori infection is a potential factor of AS. However, the underlying mechanism of H. pylori or their products cross the epithelial barriers to enter the blood circulation remains unclear. Recent studies have shown that the extracellular vesicles (EVs) derived from H. pylori-infected gastric epithelial cells encapsulated H. pylori virulence factor cytotoxin-associated gene A (CagA) and existed in the blood samples of patients or mice, which indicating that they can carry CagA into the blood circulation. Based on these findings, some researchers proposed a hypothesis that H. pylori is involved in the pathogenesis of AS via EVs-based mechanisms. In addition, outer membrane vesicles (OMVs) serve as transport vehicles to deliver H. pylori virulence factors to epithelial cells. It is necessary to discuss the role of H. pylori OMVs in the development of AS. OBJECTIVES This review will focus on the correlation between H. pylori infection and AS and tried to unveil the possible role of EVs from H. pylori-infected cells and H. pylori OMVs in the pathogenesis of AS, with a view to providing help in refining our knowledge in this aspect. METHODS All of information included in this review was retrieved from published studies on H. pylori infection in AS. RESULTS H. pylori infection may be an atherosclerotic risk factor and drives researchers to reevaluate the role of H. pylori in the pathogenesis of AS. Some findings proposed a new hypothesis that H. pylori may be involved in the pathogenesis of AS through EVs-based mechanisms. Besides EVs from H. pylori-infected cells, whether H. pylori OMVs may play some role in the pathogenesis of AS is still remain unclear. CONCLUSION Existing epidemiological and clinical evidence had shown that there is a possible association between H. pylori and AS. However, except for the larger randomized controlled trials, more basic research about EVs from H. pylori-infected cells and H. pylori OMVs is the need of the hour to unveil the possible role of H. pylori infection in the pathogenesis of AS.
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Affiliation(s)
- Liming Qiang
- Department of Gastroenterology, West China-Guang'an Hospital, Sichuan University, Guang'an, China
| | - Jianguo Hu
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Mingyuan Tian
- Department of Endocrinology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yu Li
- Clinical Medical College, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Chao Ren
- Clinical Medical College, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Yi Deng
- Clinical Medical College, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Yuan Jiang
- Clinical Medical College, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
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29
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Chen J, Zhang H, Wang S, Du Y, Wei B, Wu Q, Wang H. Inhibitors of Bacterial Extracellular Vesicles. Front Microbiol 2022; 13:835058. [PMID: 35283837 PMCID: PMC8905621 DOI: 10.3389/fmicb.2022.835058] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Accepted: 01/25/2022] [Indexed: 01/22/2023] Open
Abstract
Both Gram-positive and Gram-negative bacteria can secrete extracellular vesicles (EVs), which contain numerous active substances. EVs mediate bacterial interactions with their hosts or other microbes. Bacterial EVs play a double-edged role in infections through various mechanisms, including the delivery of virulence factors, modulating immune responses, mediating antibiotic resistance, and inhibiting competitive microbes. The spread of antibiotic resistance continues to represent a difficult clinical challenge. Therefore, the investigation of novel therapeutics is a valuable research endeavor for targeting antibiotic-resistant bacterial infections. As a pathogenic substance of bacteria, bacterial EVs have gained increased attention. Thus, EV inhibitors are expected to function as novel antimicrobial agents. The inhibition of EV production, EV activity, and EV-stimulated inflammation are considered potential pathways. This review primarily introduces compounds that effectively inhibit bacterial EVs and evaluates the prospects of their application.
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Affiliation(s)
- Jianwei Chen
- College of Pharmaceutical Science and Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, China.,State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Taipa, Macau SAR, China
| | - Hongfang Zhang
- College of Pharmaceutical Science and Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, China
| | - Siqi Wang
- College of Pharmaceutical Science and Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, China
| | - Yujie Du
- College of Pharmaceutical Science and Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, China
| | - Bin Wei
- College of Pharmaceutical Science and Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, China
| | - Qiang Wu
- State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Taipa, Macau SAR, China
| | - Hong Wang
- College of Pharmaceutical Science and Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, China.,Key Laboratory of Marine Fishery Resources Exploitment and Utilization of Zhejiang Province, Zhejiang University of Technology, Hangzhou, China
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30
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Jiang J, Mei J, Ma Y, Jiang S, Zhang J, Yi S, Feng C, Liu Y, Liu Y. Tumor hijacks macrophages and microbiota through extracellular vesicles. EXPLORATION (BEIJING, CHINA) 2022; 2:20210144. [PMID: 37324578 PMCID: PMC10190998 DOI: 10.1002/exp.20210144] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Accepted: 11/16/2021] [Indexed: 06/17/2023]
Abstract
The tumor microenvironment (TME) is a biological system with sophisticated constituents. In addition to tumor cells, tumor-associated macrophages (TAMs) and microbiota are also dominant components. The phenotypic and functional changes of TAMs are widely considered to be related to most tumor progressions. The chronic colonization of pathogenic microbes and opportunistic pathogens accounts for the generation and development of tumors. As messengers of cell-to-cell communication, tumor-derived extracellular vesicles (TDEVs) can transfer various malignant factors, regulating physiological and pathological changes in the recipients and affecting TAMs and microbes in the TME. Despite the new insights into tumorigenesis and progress brought by the above factors, the crosstalk among tumor cells, macrophages, and microbiota remain elusive, and few studies have focused on how TDEVs act as an intermediary. We reviewed how tumor cells recruit and domesticate macrophages and microbes through extracellular vehicles and how hijacked macrophages and microbiota interact with tumor-promoting feedback, achieving a reciprocal coexistence under the TME and working together to facilitate tumor progression. It is significant to seek evidence to clarify those specific interactions and reveal therapeutic targets to curb tumor progression and improve prognosis.
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Affiliation(s)
- Jipeng Jiang
- Postgraduate School Medical School of Chinese PLA Beijing P. R. China
- Department of Thoracic Surgery The First Medical Center of Chinese PLA General Hospital Beijing P. R. China
| | - Jie Mei
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology of China Beijing P. R. China
- University of Chinese Academy of Science Beijing P. R. China
| | - Yongfu Ma
- Department of Thoracic Surgery The First Medical Center of Chinese PLA General Hospital Beijing P. R. China
| | - Shasha Jiang
- Postgraduate School Medical School of Chinese PLA Beijing P. R. China
- Department of Thoracic Surgery The First Medical Center of Chinese PLA General Hospital Beijing P. R. China
| | - Jian Zhang
- Department of Thoracic Surgery The First Medical Center of Chinese PLA General Hospital Beijing P. R. China
| | - Shaoqiong Yi
- Department of Thoracic Surgery The First Medical Center of Chinese PLA General Hospital Beijing P. R. China
| | - Changjiang Feng
- Department of Thoracic Surgery The First Medical Center of Chinese PLA General Hospital Beijing P. R. China
| | - Yang Liu
- Postgraduate School Medical School of Chinese PLA Beijing P. R. China
- Department of Thoracic Surgery The First Medical Center of Chinese PLA General Hospital Beijing P. R. China
| | - Ying Liu
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology of China Beijing P. R. China
- GBA National Institute for Nanotechnology Innovation Guangdong P. R. China
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31
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Outer Membrane Vesicles (OMVs) of Pseudomonas aeruginosa Provide Passive Resistance but Not Sensitization to LPS-Specific Phages. Viruses 2022; 14:v14010121. [PMID: 35062325 PMCID: PMC8778925 DOI: 10.3390/v14010121] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 01/05/2022] [Accepted: 01/06/2022] [Indexed: 02/06/2023] Open
Abstract
Outer membrane vesicles (OMVs) released from gram-negative bacteria are key elements in bacterial physiology, pathogenesis, and defence. In this study, we investigated the role of Pseudomonas aeruginosa OMVs in the anti-phage defence as well as in the potential sensitization to LPS-specific phages. Using transmission electron microscopy, virion infectivity, and neutralization assays, we have shown that both phages efficiently absorb on free vesicles and are unable to infect P. aeruginosa host. Nevertheless, the accompanying decrease in PFU titre (neutralization) was only observed for myovirus KT28 but not podovirus LUZ7. Next, we verified whether OMVs derived from wild-type PAO1 strain can sensitize the LPS-deficient mutant (Δwbpl PAO1) resistant to tested phages. The flow cytometry experiments proved a quite effective and comparable association of OMVs to Δwbpl PAO1 and wild-type PAO1; however, the growth kinetic curves and one-step growth assay revealed no sensitization event of the OMV-associated phage-resistant P. aeruginosa deletant to LPS-specific phages. Our findings for the first time identify naturally formed OMVs as important players in passive resistance (protection) of P. aeruginosa population to phages, but we disproved the hypothesis of transferring phage receptors to make resistant strains susceptible to LPS-dependent phages.
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32
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Delivery of Toxins and Effectors by Bacterial Membrane Vesicles. Toxins (Basel) 2021; 13:toxins13120845. [PMID: 34941684 PMCID: PMC8703475 DOI: 10.3390/toxins13120845] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 11/22/2021] [Accepted: 11/23/2021] [Indexed: 01/22/2023] Open
Abstract
Pathogenic bacteria interact with cells of their host via many factors. The surface components, i.e., adhesins, lipoproteins, LPS and glycoconjugates, are particularly important in the initial stages of colonization. They enable adhesion and multiplication, as well as the formation of biofilms. In contrast, virulence factors such as invasins and toxins act quickly to damage host cells, causing tissue destruction and, consequently, organ dysfunction. These proteins must be exported from the bacterium and delivered to the host cell in order to function effectively. Bacteria have developed a number of one- and two-step secretion systems to transport their proteins to target cells. Recently, several authors have postulated the existence of another transport system (sometimes called "secretion system type zero"), which utilizes extracellular structures, namely membrane vesicles (MVs). This review examines the role of MVs as transporters of virulence factors and the interaction of toxin-containing vesicles and other protein effectors with different human cell types. We focus on the unique ability of vesicles to cross the blood-brain barrier and deliver protein effectors from intestinal or oral bacteria to the central nervous system.
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33
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Tiku V, Tan MW. Host immunity and cellular responses to bacterial outer membrane vesicles. Trends Immunol 2021; 42:1024-1036. [PMID: 34635395 DOI: 10.1016/j.it.2021.09.006] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Revised: 09/12/2021] [Accepted: 09/14/2021] [Indexed: 01/18/2023]
Abstract
All Gram-negative bacteria produce outer membrane vesicles (OMVs) which are minute spherical structures emanating from the bacterial outer membrane. OMVs are primarily enriched in lipopolysaccharide (LPS) and phospholipids, as well as outer membrane and periplasmic proteins. Recent research has provided convincing evidence for their role in multiple aspects of bacterial physiology and their interaction with vertebrate host cells. OMVs play vital roles in bacterial colonization, delivery of virulence factors, and disease pathogenesis. Here, we discuss the interactions of OMVs with mammalian host cells with a focus on how bacteria use OMVs to modulate host immune responses that eventually enable bacteria to evade host immunity.
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Affiliation(s)
- Varnesh Tiku
- Department of Infectious Diseases, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
| | - Man-Wah Tan
- Department of Infectious Diseases, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
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34
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Zingl FG, Leitner DR, Thapa HB, Schild S. Outer membrane vesicles as versatile tools for therapeutic approaches. MICROLIFE 2021; 2:uqab006. [PMID: 37223254 PMCID: PMC10117751 DOI: 10.1093/femsml/uqab006] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Accepted: 06/05/2021] [Indexed: 05/25/2023]
Abstract
Budding of the bacterial surface results in the formation and secretion of outer membrane vesicles, which is a conserved phenomenon observed in Gram-negative bacteria. Recent studies highlight that these sphere-shaped facsimiles of the donor bacterium's surface with enclosed periplasmic content may serve multiple purposes for their host bacterium. These include inter- and intraspecies cell-cell communication, effector delivery to target cells and bacterial adaptation strategies. This review provides a concise overview of potential medical applications to exploit outer membrane vesicles for therapeutic approaches. Due to the fact that outer membrane vesicles resemble the surface of their donor cells, they represent interesting nonliving candidates for vaccine development. Furthermore, bacterial donor species can be genetically engineered to display various proteins and glycans of interest on the outer membrane vesicle surface or in their lumen. Outer membrane vesicles also possess valuable bioreactor features as they have the natural capacity to protect, stabilize and enhance the activity of luminal enzymes. Along these features, outer membrane vesicles not only might be suitable for biotechnological applications but may also enable cell-specific delivery of designed therapeutics as they are efficiently internalized by nonprofessional phagocytes. Finally, outer membrane vesicles are potent modulators of our immune system with pro- and anti-inflammatory properties. A deeper understanding of immunoregulatory effects provoked by different outer membrane vesicles is the basis for their possible future applications ranging from inflammation and immune response modulation to anticancer therapy.
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Affiliation(s)
- Franz G Zingl
- Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50, 8010 Graz, Austria
| | - Deborah R Leitner
- Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50, 8010 Graz, Austria
| | - Himadri B Thapa
- Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50, 8010 Graz, Austria
| | - Stefan Schild
- Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50, 8010 Graz, Austria
- BioTechMed-Graz, Austria
- Field of Excellence BioHealth, University of Graz, 8010 Graz, Austria
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35
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Dhital S, Deo P, Stuart I, Naderer T. Bacterial outer membrane vesicles and host cell death signaling. Trends Microbiol 2021; 29:1106-1116. [PMID: 34001418 DOI: 10.1016/j.tim.2021.04.003] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 04/20/2021] [Accepted: 04/21/2021] [Indexed: 12/16/2022]
Abstract
The programmed cell death pathways of pyroptosis and apoptosis protect mammals from infections. The activation of host cell death signaling depends on cell surface and cytosolic receptors that bind bacterial molecules or sense their activity. The formation of cytosolic protein complexes, such as the inflammasome and apoptosome, activates caspases, pore-forming proteins, and inflammatory cytokines. These pathways respond to bacteria and their released membrane vesicles. Outer membrane vesicles (OMVs) that emerge from the outer membrane of Gram-negative bacteria deliver a range of bacterial molecules, including lipids, proteins, polysaccharides and nucleic acids to host cells. Recent findings describe how OMV-associated molecules activate pyroptosis, apoptosis, and other inflammatory pathways. We discuss here how OMV-associated molecules are sensed by the immune system and how this contributes to infections and inflammatory diseases.
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Affiliation(s)
- Subhash Dhital
- Department of Biochemistry & Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton 3800, Australia
| | - Pankaj Deo
- Department of Biochemistry & Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton 3800, Australia
| | - Isabella Stuart
- Department of Biochemistry & Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton 3800, Australia
| | - Thomas Naderer
- Department of Biochemistry & Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton 3800, Australia.
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González MF, Díaz P, Sandoval-Bórquez A, Herrera D, Quest AFG. Helicobacter pylori Outer Membrane Vesicles and Extracellular Vesicles from Helicobacter pylori-Infected Cells in Gastric Disease Development. Int J Mol Sci 2021; 22:ijms22094823. [PMID: 34062919 PMCID: PMC8124820 DOI: 10.3390/ijms22094823] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 03/31/2021] [Accepted: 04/02/2021] [Indexed: 02/08/2023] Open
Abstract
Extracellular vesicles (EVs) are cell-derived vesicles important in intercellular communication that play an essential role in host-pathogen interactions, spreading pathogen-derived as well as host-derived molecules during infection. Pathogens can induce changes in the composition of EVs derived from the infected cells and use them to manipulate their microenvironment and, for instance, modulate innate and adaptive inflammatory immune responses, both in a stimulatory or suppressive manner. Gastric cancer is one of the leading causes of cancer-related deaths worldwide and infection with Helicobacter pylori (H. pylori) is considered the main risk factor for developing this disease, which is characterized by a strong inflammatory component. EVs released by host cells infected with H. pylori contribute significantly to inflammation, and in doing so promote the development of disease. Additionally, H. pylori liberates vesicles, called outer membrane vesicles (H. pylori-OMVs), which contribute to atrophia and cell transformation in the gastric epithelium. In this review, the participation of both EVs from cells infected with H. pylori and H. pylori-OMVs associated with the development of gastric cancer will be discussed. By deciphering which functions of these external vesicles during H. pylori infection benefit the host or the pathogen, novel treatment strategies may become available to prevent disease.
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Affiliation(s)
- María Fernanda González
- Center for studies on Exercise, Metabolism and Cancer (CEMC), Laboratory of Cellular Communication, Program of Cell and Molecular Biology, Faculty of Medicine, Institute of Biomedical Sciences (ICBM), Universidad de Chile, Santiago 8380453, Chile; (M.F.G.); (P.D.); (A.S.-B.); (D.H.)
- Advanced Center for Chronic Diseases (ACCDiS), Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile
| | - Paula Díaz
- Center for studies on Exercise, Metabolism and Cancer (CEMC), Laboratory of Cellular Communication, Program of Cell and Molecular Biology, Faculty of Medicine, Institute of Biomedical Sciences (ICBM), Universidad de Chile, Santiago 8380453, Chile; (M.F.G.); (P.D.); (A.S.-B.); (D.H.)
- Advanced Center for Chronic Diseases (ACCDiS), Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile
| | - Alejandra Sandoval-Bórquez
- Center for studies on Exercise, Metabolism and Cancer (CEMC), Laboratory of Cellular Communication, Program of Cell and Molecular Biology, Faculty of Medicine, Institute of Biomedical Sciences (ICBM), Universidad de Chile, Santiago 8380453, Chile; (M.F.G.); (P.D.); (A.S.-B.); (D.H.)
- Advanced Center for Chronic Diseases (ACCDiS), Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile
| | - Daniela Herrera
- Center for studies on Exercise, Metabolism and Cancer (CEMC), Laboratory of Cellular Communication, Program of Cell and Molecular Biology, Faculty of Medicine, Institute of Biomedical Sciences (ICBM), Universidad de Chile, Santiago 8380453, Chile; (M.F.G.); (P.D.); (A.S.-B.); (D.H.)
- Advanced Center for Chronic Diseases (ACCDiS), Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile
| | - Andrew F. G. Quest
- Center for studies on Exercise, Metabolism and Cancer (CEMC), Laboratory of Cellular Communication, Program of Cell and Molecular Biology, Faculty of Medicine, Institute of Biomedical Sciences (ICBM), Universidad de Chile, Santiago 8380453, Chile; (M.F.G.); (P.D.); (A.S.-B.); (D.H.)
- Advanced Center for Chronic Diseases (ACCDiS), Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile
- Corporación Centro de Estudios Científicos de las Enfermedades Crónicas (CECEC), Santiago 7680201, Chile
- Correspondence: ; Tel.: +56-2-29786832
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Outer Membrane Vesicle Production by Helicobacter pylori Represents an Approach for the Delivery of Virulence Factors CagA, VacA and UreA into Human Gastric Adenocarcinoma (AGS) Cells. Int J Mol Sci 2021; 22:ijms22083942. [PMID: 33920443 PMCID: PMC8069053 DOI: 10.3390/ijms22083942] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 04/07/2021] [Accepted: 04/09/2021] [Indexed: 01/18/2023] Open
Abstract
Helicobacter pylori infection is the etiology of several gastric-related diseases including gastric cancer. Cytotoxin associated gene A (CagA), vacuolating cytotoxin A (VacA) and α-subunit of urease (UreA) are three major virulence factors of H. pylori, and each of them has a distinct entry pathway and pathogenic mechanism during bacterial infection. H. pylori can shed outer membrane vesicles (OMVs). Therefore, it would be interesting to explore the production kinetics of H. pylori OMVs and its connection with the entry of key virulence factors into host cells. Here, we isolated OMVs from H. pylori 26,695 strain and characterized their properties and interaction kinetics with human gastric adenocarcinoma (AGS) cells. We found that the generation of OMVs and the presence of CagA, VacA and UreA in OMVs were a lasting event throughout different phases of bacterial growth. H. pylori OMVs entered AGS cells mainly through macropinocytosis/phagocytosis. Furthermore, CagA, VacA and UreA could enter AGS cells via OMVs and the treatment with H. pylori OMVs would cause cell death. Comparison of H. pylori 26,695 and clinical strains suggested that the production and characteristics of OMVs are not only limited to laboratory strains commonly in use, but a general phenomenon to most H. pylori strains.
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Gilmore WJ, Johnston EL, Zavan L, Bitto NJ, Kaparakis-Liaskos M. Immunomodulatory roles and novel applications of bacterial membrane vesicles. Mol Immunol 2021; 134:72-85. [PMID: 33725501 DOI: 10.1016/j.molimm.2021.02.027] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Revised: 02/15/2021] [Accepted: 02/24/2021] [Indexed: 12/19/2022]
Abstract
Bacteria release extracellular vesicles (EVs) known as bacterial membrane vesicles (BMVs) during their normal growth. Gram-negative bacteria produce BMVs termed outer membrane vesicles (OMVs) that are composed of a range of biological cargo and facilitate numerous bacterial functions, including promoting pathogenesis and mediating disease in the host. By contrast, less is understood about BMVs produced by Gram-positive bacteria, which are referred to as membrane vesicles (MVs), however their contribution to mediating bacterial pathogenesis has recently become evident. In this review, we summarise the mechanisms whereby BMVs released by Gram-negative and Gram-positive bacteria are produced, in addition to discussing their key functions in promoting bacterial survival, mediating pathogenesis and modulating host immune responses. Furthermore, we discuss the mechanisms whereby BMVs produced by both commensal and pathogenic organisms can enter host cells and interact with innate immune receptors, in addition to how they modulate host innate and adaptive immunity to promote immunotolerance or drive the onset and progression of disease. Finally, we highlight current and emerging applications of BMVs in vaccine design, biotechnology and cancer therapeutics.
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Affiliation(s)
- William J Gilmore
- Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, VIC, Australia; Research Centre for Extracellular Vesicles, School of Molecular Science, La Trobe University, Melbourne, VIC, Australia
| | - Ella L Johnston
- Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, VIC, Australia; Research Centre for Extracellular Vesicles, School of Molecular Science, La Trobe University, Melbourne, VIC, Australia
| | - Lauren Zavan
- Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, VIC, Australia; Research Centre for Extracellular Vesicles, School of Molecular Science, La Trobe University, Melbourne, VIC, Australia
| | - Natalie J Bitto
- Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, VIC, Australia; Research Centre for Extracellular Vesicles, School of Molecular Science, La Trobe University, Melbourne, VIC, Australia
| | - Maria Kaparakis-Liaskos
- Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, VIC, Australia; Research Centre for Extracellular Vesicles, School of Molecular Science, La Trobe University, Melbourne, VIC, Australia.
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Abstract
The release of extracellular vesicles (EVs) is a process conserved across the three domains of life. Amongst prokaryotes, EVs produced by Gram-negative bacteria, termed outer membrane vesicles (OMVs), were identified more than 50 years ago and a wealth of literature exists regarding their biogenesis, composition and functions. OMVs have been implicated in benefiting numerous metabolic functions of their parent bacterium. Additionally, OMVs produced by pathogenic bacteria have been reported to contribute to pathology within the disease setting. By contrast, the release of EVs from Gram-positive bacteria, known as membrane vesicles (MVs), has only been widely accepted within the last decade. As such, there is a significant disproportion in knowledge regarding MVs compared to OMVs. Here we provide an overview of the literature regarding bacterial membrane vesicles (BMVs) produced by pathogenic and commensal bacteria. We highlight the mechanisms of BMV biogenesis and their roles in assisting bacterial survival, in addition to discussing their functions in promoting disease pathologies and their potential use as novel therapeutic strategies.
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Affiliation(s)
- William J Gilmore
- Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, VIC, Australia
- Research Centre for Extracellular Vesicles, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC, Australia
| | - Natalie J Bitto
- Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, VIC, Australia
- Research Centre for Extracellular Vesicles, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC, Australia
| | - Maria Kaparakis-Liaskos
- Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, VIC, Australia.
- Research Centre for Extracellular Vesicles, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC, Australia.
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Jarzab M, Posselt G, Meisner-Kober N, Wessler S. Helicobacter pylori-Derived Outer Membrane Vesicles (OMVs): Role in Bacterial Pathogenesis? Microorganisms 2020; 8:E1328. [PMID: 32878302 PMCID: PMC7564109 DOI: 10.3390/microorganisms8091328] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Revised: 08/24/2020] [Accepted: 08/31/2020] [Indexed: 01/06/2023] Open
Abstract
Persistent infections with the human pathogen Helicobacter pylori (H. pylori) have been closely associated with the induction and progression of a wide range of gastric disorders, including acute and chronic gastritis, ulceration in the stomach and duodenum, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric adenocarcinoma. The pathogenesis of H. pylori is determined by a complicated network of manifold mechanisms of pathogen-host interactions, which involves a coordinated interplay of H. pylori pathogenicity and virulence factors with host cells. While these molecular and cellular mechanisms have been intensively investigated to date, the knowledge about outer membrane vesicles (OMVs) derived from H. pylori and their implication in bacterial pathogenesis is not well developed. In this review, we summarize the current knowledge on H. pylori-derived OMVs.
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Affiliation(s)
- Miroslaw Jarzab
- Division of Microbiology, Department of Biosciences, Paris-Lodron University of Salzburg, 5020 Salzburg, Austria; (M.J.); (G.P.)
| | - Gernot Posselt
- Division of Microbiology, Department of Biosciences, Paris-Lodron University of Salzburg, 5020 Salzburg, Austria; (M.J.); (G.P.)
| | - Nicole Meisner-Kober
- Division of Chemical Biology and Biological Therapeutics, Department of Biosciences, Paris-Lodron University of Salzburg, 5020 Salzburg, Austria;
| | - Silja Wessler
- Division of Microbiology, Department of Biosciences, Paris-Lodron University of Salzburg, 5020 Salzburg, Austria; (M.J.); (G.P.)
- Cancer Cluster Salzburg, Allergy-Cancer-BioNano Research Centre and, Paris-Lodron University of Salzburg, 5020 Salzburg, Austria
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41
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Murray BO, Dawson RA, Alsharaf LM, Anne Winter J. Protective effects of Helicobacter pylori membrane vesicles against stress and antimicrobial agents. MICROBIOLOGY (READING, ENGLAND) 2020; 166:751-758. [PMID: 32463354 PMCID: PMC7641381 DOI: 10.1099/mic.0.000934] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Accepted: 05/01/2020] [Indexed: 12/11/2022]
Abstract
Outer-membrane vesicles (OMVs) produced by Helicobacter pylori deliver bacterial components to host cells, provide a mechanism for stabilization of secreted components and may allow the bacteria to exert 'long-range' effects in the gastric niche, promoting persistence. In addition to their well-characterized host cell interactions, membrane vesicles improve stress survival in other bacterial species, and are constitutively produced by both pathogenic and non-pathogenic bacteria. We aimed to determine whether OMVs could improve H. pylori survival of a range of stressors. The effects of purified OMVs on the resistance of H. pylori to a range of environmental and antimicrobial stresses were determined using growth curves and survival assays. Addition of purified OMVs to H. pylori cultures provided dose-dependent protection against hydrogen peroxide-mediated killing. Supplementation with OMVs also partially protected H. pylori against the bactericidal effects of the antibiotics clarithromycin and levofloxacin, but not against amoxicillin nor metronidazole. Addition of purified OMVs allowed H. pylori to grow in the presence of inhibitory concentrations of the antimicrobial peptide LL-37. In the presence of 50 µg OMVs ml-1, significantly enhanced H. pylori growth was observed at higher LL-37 concentrations compared with lower LL-37 concentrations, suggesting that OMV-LL-37 interactions might facilitate release of growth-promoting nutrients. Taken together, these data indicate that production of membrane vesicles could help H. pylori to survive exposure to antibiotics and host antimicrobial defences during infection.
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Affiliation(s)
- Benjamin Oliver Murray
- School of Science and Technology, Nottingham Trent University, Nottingham, NG11 8NS, UK
- Centre for Urological Biology, Department of Renal Medicine, Division of Medicine, University College London, London, UK
| | - Robin Andrew Dawson
- School of Science and Technology, Nottingham Trent University, Nottingham, NG11 8NS, UK
- School of Environmental Sciences, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK
| | - Lolwah Mohammad Alsharaf
- School of Science and Technology, Nottingham Trent University, Nottingham, NG11 8NS, UK
- Al-Amiri Hospital, Ministry of Health, Kuwait City, Kuwait
| | - Jody Anne Winter
- School of Science and Technology, Nottingham Trent University, Nottingham, NG11 8NS, UK
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Tsai YL, Tsai WC, Qing Z, Chang CJ. Dichotomous effects of microbial membrane vesicles on the regulation of immunity. MEDICINE IN MICROECOLOGY 2020. [DOI: 10.1016/j.medmic.2020.100009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
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Johnston EL, Kufer TA, Kaparakis-Liaskos M. Immunodetection and Pathogenesis Mediated by Bacterial Membrane Vesicles. BACTERIAL MEMBRANE VESICLES 2020:159-188. [DOI: 10.1007/978-3-030-36331-4_8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Ansari S, Yamaoka Y. Helicobacter pylori Virulence Factors Exploiting Gastric Colonization and its Pathogenicity. Toxins (Basel) 2019; 11:677. [PMID: 31752394 PMCID: PMC6891454 DOI: 10.3390/toxins11110677] [Citation(s) in RCA: 144] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Revised: 11/15/2019] [Accepted: 11/16/2019] [Indexed: 02/07/2023] Open
Abstract
Helicobacter pylori colonizes the gastric epithelial cells of at least half of the world's population, and it is the strongest risk factor for developing gastric complications like chronic gastritis, ulcer diseases, and gastric cancer. To successfully colonize and establish a persistent infection, the bacteria must overcome harsh gastric conditions. H. pylori has a well-developed mechanism by which it can survive in a very acidic niche. Despite bacterial factors, gastric environmental factors and host genetic constituents together play a co-operative role for gastric pathogenicity. The virulence factors include bacterial colonization factors BabA, SabA, OipA, and HopQ, and the virulence factors necessary for gastric pathogenicity include the effector proteins like CagA, VacA, HtrA, and the outer membrane vesicles. Bacterial factors are considered more important. Here, we summarize the recent information to better understand several bacterial virulence factors and their role in the pathogenic mechanism.
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Affiliation(s)
- Shamshul Ansari
- Department of Microbiology, Chitwan Medical College and Teaching Hospital, Bharatpur 44200, Chitwan, Nepal;
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Idaigaoka, Hasama-machi, Yufu, Oita 879-5593, Japan
- Global Oita Medical Advanced Research Center for Health, Idaigaoka, Hasama-machi, Yufu, Oita 879-5593, Japan
- Department of Medicine, Gastroenterology and Hepatology Section, Baylor College of Medicine, 2002 Holcombe Blvd., Houston, TX 77030, USA
- Borneo Medical and Health Research Centre, Universiti Malaysia Sabah, Kota Kinabaru, Sabah 88400, Malaysia
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Ephrin-A5 potentiates netrin-1 axon guidance by enhancing Neogenin availability. Sci Rep 2019; 9:12009. [PMID: 31427645 PMCID: PMC6700147 DOI: 10.1038/s41598-019-48519-0] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2019] [Accepted: 08/07/2019] [Indexed: 01/22/2023] Open
Abstract
Axonal growth cones are guided by molecular cues in the extracellular environment. The mechanisms of combinatorial integration of guidance signals at the growth cone cell membrane are still being unravelled. Limb-innervating axons of vertebrate spinal lateral motor column (LMC) neurons are attracted to netrin-1 via its receptor, Neogenin, and are repelled from ephrin-A5 through its receptor EphA4. The presence of both cues elicits synergistic guidance of LMC axons, but the mechanism of this effect remains unknown. Using fluorescence immunohistochemistry, we show that ephrin-A5 increases LMC growth cone Neogenin protein levels and netrin-1 binding. This effect is enhanced by overexpressing EphA4 and is inhibited by blocking ephrin-A5-EphA4 binding. These effects have a functional consequence on LMC growth cone responses since bath addition of ephrin-A5 increases the responsiveness of LMC axons to netrin-1. Surprisingly, the overexpression of EphA4 lacking its cytoplasmic tail, also enhances Neogenin levels at the growth cone and potentiates LMC axon preference for growth on netrin-1. Since netrins and ephrins participate in a wide variety of biological processes, the enhancement of netrin-1 signalling by ephrins may have broad implications.
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Cryo-EM structures of Helicobacter pylori vacuolating cytotoxin A oligomeric assemblies at near-atomic resolution. Proc Natl Acad Sci U S A 2019; 116:6800-6805. [PMID: 30894496 PMCID: PMC6452728 DOI: 10.1073/pnas.1821959116] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
Helicobacter pylori infects nearly half of the world’s population and is the primary cause of various gastric diseases. It has evolved various virulence factors to aid its host colonization and infection, including the vacuolating cytotoxin A (VacA) that is responsible for the pathogenesis of H. pylori-related diseases. Here, we resolve multiple structures of the water-soluble VacA oligomeric assemblies using cryoelectron microscopy (cryo-EM) at near-atomic resolution. These studies suggest a model of structural changes of functional VacA hexamer needed for the pore-formation process across the membrane and highlight the capability of cryo-EM to resolve multiple structure snapshots from a single specimen at near-atomic resolution. Human gastric pathogen Helicobacter pylori (H. pylori) is the primary risk factor for gastric cancer and is one of the most prevalent carcinogenic infectious agents. Vacuolating cytotoxin A (VacA) is a key virulence factor secreted by H. pylori and induces multiple cellular responses. Although structural and functional studies of VacA have been extensively performed, the high-resolution structure of a full-length VacA protomer and the molecular basis of its oligomerization are still unknown. Here, we use cryoelectron microscopy to resolve 10 structures of VacA assemblies, including monolayer (hexamer and heptamer) and bilayer (dodecamer, tridecamer, and tetradecamer) oligomers. The models of the 88-kDa full-length VacA protomer derived from the near-atomic resolution maps are highly conserved among different oligomers and show a continuous right-handed β-helix made up of two domains with extensive domain–domain interactions. The specific interactions between adjacent protomers in the same layer stabilizing the oligomers are well resolved. For double-layer oligomers, we found short- and/or long-range hydrophobic interactions between protomers across the two layers. Our structures and other previous observations lead to a mechanistic model wherein VacA hexamer would correspond to the prepore-forming state, and the N-terminal region of VacA responsible for the membrane insertion would undergo a large conformational change to bring the hydrophobic transmembrane region to the center of the oligomer for the membrane channel formation.
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Cecil JD, Sirisaengtaksin N, O'Brien-Simpson NM, Krachler AM. Outer Membrane Vesicle-Host Cell Interactions. Microbiol Spectr 2019; 7:10.1128/microbiolspec.psib-0001-2018. [PMID: 30681067 PMCID: PMC6352913 DOI: 10.1128/microbiolspec.psib-0001-2018] [Citation(s) in RCA: 111] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2018] [Indexed: 02/06/2023] Open
Abstract
Outer membrane vesicles (OMVs) are nanosized proteoliposomes derived from the outer membrane of Gram-negative bacteria. They are ubiquitously produced both in culture and during infection and are now recognized to play crucial roles during host-microbe interactions. OMVs can transport a broad range of chemically diverse cargoes, including lipids and lipopolysaccharides, membrane-embedded and associated proteins and small molecules, peptidoglycan, and nucleic acids. Particularly, virulence factors such as adhesins and toxins are often enriched in OMVs. Here we discuss a variety of ways in which OMVs facilitate host-microbe interactions, including their contributions to biofilm formation, nutrient scavenging, and modulation of host cell function. We particularly examine recent findings regarding OMV-host cell interactions in the oral cavity and the gastrointestinal tract.
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Affiliation(s)
- Jessica D Cecil
- Oral Health Cooperative Research Centre, Melbourne Dental School, Bio21 Institute, The University of Melbourne, Melbourne, Victoria 3052, Australia
- *These authors contributed equally
| | - Natalie Sirisaengtaksin
- Department of Microbiology and Molecular Genetics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030
- *These authors contributed equally
| | - Neil M O'Brien-Simpson
- Oral Health Cooperative Research Centre, Melbourne Dental School, Bio21 Institute, The University of Melbourne, Melbourne, Victoria 3052, Australia
| | - Anne Marie Krachler
- Department of Microbiology and Molecular Genetics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030
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Cai W, Kesavan DK, Wan J, Abdelaziz MH, Su Z, Xu H. Bacterial outer membrane vesicles, a potential vaccine candidate in interactions with host cells based. Diagn Pathol 2018; 13:95. [PMID: 30537996 PMCID: PMC6290530 DOI: 10.1186/s13000-018-0768-y] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2018] [Accepted: 11/07/2018] [Indexed: 02/07/2023] Open
Abstract
Both Gram-Positive and Gram-Negative bacteria can secrete outer membrane vesicles (OMVs) in their growth and metabolism process. Originally, OMVs were considered as a by-product of bacterial merisis. However, many scientists have reported the important role of OMVs in many fields recently. In this review, we briefly introduce OMVs biological functions and then summarize the findings about the OMVs interactions with host cells. At last, we will make an expectation about the prospects of the application of OMVs as vaccines.
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Affiliation(s)
- Wei Cai
- Department of Immunology, Jiangsu University, Zhenjiang, 212013, Jiangsu, China
| | | | - Jie Wan
- Department of Immunology, Jiangsu University, Zhenjiang, 212013, Jiangsu, China
| | | | - Zhaoliang Su
- Department of Immunology, Jiangsu University, Zhenjiang, 212013, Jiangsu, China.,The Central Laboratory, the Fourth Affiliated of Jiangsu University, Zhenjiang, 212001, China
| | - Huaxi Xu
- Department of Immunology, Jiangsu University, Zhenjiang, 212013, Jiangsu, China.
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49
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Chmiela M, Walczak N, Rudnicka K. Helicobacter pylori outer membrane vesicles involvement in the infection development and Helicobacter pylori-related diseases. J Biomed Sci 2018; 25:78. [PMID: 30409143 PMCID: PMC6225681 DOI: 10.1186/s12929-018-0480-y] [Citation(s) in RCA: 50] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2018] [Accepted: 10/24/2018] [Indexed: 02/07/2023] Open
Abstract
Helicobacter pylori - (H. pylori) play a role in the pathogenesis of gastritis, gastric and duodenal ulcers as well as gastric cancer. A possible involvement of outer membrane vesicles (OMVs) produced by H. pylori in the distribution of bacterial antigens through the gastric epithelial barrier and their role in the development of local and systemic host inflammatory and immune responses has been suggested. OMVs contain various biologically active compounds, which internalize into host cells affecting signaling pathways and promoting apoptosis of gastric epithelial and immunocompetent cells. OMVs-associated H. pylori virulence factors may strengthen or downregulate the immune responses leading to disease development. This review describes the biological importance of H. pylori OMVs and their role in the course of H. pylori infections, as well as H. pylori related local and systemic effects.
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Affiliation(s)
- Magdalena Chmiela
- Laboratory of Gastroimmunology, Department of Immunology and Infectious Biology, Faculty of Biology and Environmental Protection, University of Łódź, Banacha 12/16, 90-237, Łódź, Poland
| | - Natalia Walczak
- Laboratory of Gastroimmunology, Department of Immunology and Infectious Biology, Faculty of Biology and Environmental Protection, University of Łódź, Banacha 12/16, 90-237, Łódź, Poland
| | - Karolina Rudnicka
- Laboratory of Gastroimmunology, Department of Immunology and Infectious Biology, Faculty of Biology and Environmental Protection, University of Łódź, Banacha 12/16, 90-237, Łódź, Poland.
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Bravo D, Hoare A, Soto C, Valenzuela MA, Quest AFG. Helicobacter pylori in human health and disease: Mechanisms for local gastric and systemic effects. World J Gastroenterol 2018; 24:3071-3089. [PMID: 30065554 PMCID: PMC6064966 DOI: 10.3748/wjg.v24.i28.3071] [Citation(s) in RCA: 138] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2018] [Revised: 05/17/2018] [Accepted: 06/27/2018] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) is present in roughly 50% of the human population worldwide and infection levels reach over 70% in developing countries. The infection has classically been associated with different gastro-intestinal diseases, but also with extra gastric diseases. Despite such associations, the bacterium frequently persists in the human host without inducing disease, and it has been suggested that H. pylori may also play a beneficial role in health. To understand how H. pylori can produce such diverse effects in the human host, several studies have focused on understanding the local and systemic effects triggered by this bacterium. One of the main mechanisms by which H. pylori is thought to damage the host is by inducing local and systemic inflammation. However, more recently, studies are beginning to focus on the effects of H. pylori and its metabolism on the gastric and intestinal microbiome. The objective of this review is to discuss how H. pylori has co-evolved with humans, how H. pylori presence is associated with positive and negative effects in human health and how inflammation and/or changes in the microbiome are associated with the observed outcomes.
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Affiliation(s)
- Denisse Bravo
- Oral Microbiology Laboratory, Pathology and Oral Medicine Department, Faculty of Dentistry, Universidad de Chile, Santiago 8380492, Chile
| | - Anilei Hoare
- Oral Microbiology Laboratory, Pathology and Oral Medicine Department, Faculty of Dentistry, Universidad de Chile, Santiago 8380492, Chile
| | - Cristopher Soto
- Oral Microbiology Laboratory, Pathology and Oral Medicine Department, Faculty of Dentistry, Universidad de Chile, Santiago 8380492, Chile
| | - Manuel A Valenzuela
- Advanced Center for Chronic Diseases, Institute for Health-Related Research and Innovation, Faculty of Health Sciences, Universidad Central de Chile, Santiago 8380447, Chile
| | - Andrew FG Quest
- Advanced Center for Chronic Diseases, Center for Studies on Exercise, Metabolism and Cancer, Biomedical Science Institute, Faculty of Medicine, Universidad de Chile, Santiago 8380447, Chile
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