Humans Surviving Cholera Develop Antibodies against <named-content content-type="genus-species">Vibrio cholerae</named-content> O-Specific Polysaccharide That Inhibit Pathogen Motility
ABSTRACT The mechanism of protection against cholera afforded by previous illness or vaccination is currently unknown. We have recently shown that antibodies targeting O-specific polysaccharide (OSP) of Vibrio cholerae correlate highly with protection against cholera. V. cholerae is highly motile an...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2020-12-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.02847-20 |
| _version_ | 1819004384525156352 |
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| author | Richelle C. Charles Meagan Kelly Jenny M. Tam Aklima Akter Motaher Hossain Kamrul Islam Rajib Biswas Mohammad Kamruzzaman Fahima Chowdhury Ashraful I. Khan Daniel T. Leung Ana Weil Regina C. LaRocque Taufiqur Rahman Bhuiyan Atiqur Rahman Leslie M. Mayo-Smith Rachel L. Becker Jatin M. Vyas Christina S. Faherty Kourtney P. Nickerson Samantha Giffen Alaina S. Ritter Matthew K. Waldor Peng Xu Pavol Kováč Stephen B. Calderwood Robert C. Kauffman Jens Wrammert Firdausi Qadri Jason B. Harris Edward T. Ryan |
| author_facet | Richelle C. Charles Meagan Kelly Jenny M. Tam Aklima Akter Motaher Hossain Kamrul Islam Rajib Biswas Mohammad Kamruzzaman Fahima Chowdhury Ashraful I. Khan Daniel T. Leung Ana Weil Regina C. LaRocque Taufiqur Rahman Bhuiyan Atiqur Rahman Leslie M. Mayo-Smith Rachel L. Becker Jatin M. Vyas Christina S. Faherty Kourtney P. Nickerson Samantha Giffen Alaina S. Ritter Matthew K. Waldor Peng Xu Pavol Kováč Stephen B. Calderwood Robert C. Kauffman Jens Wrammert Firdausi Qadri Jason B. Harris Edward T. Ryan |
| author_sort | Richelle C. Charles |
| collection | DOAJ |
| description | ABSTRACT The mechanism of protection against cholera afforded by previous illness or vaccination is currently unknown. We have recently shown that antibodies targeting O-specific polysaccharide (OSP) of Vibrio cholerae correlate highly with protection against cholera. V. cholerae is highly motile and possesses a flagellum sheathed in OSP, and motility of V. cholerae correlates with virulence. Using high-speed video microscopy and building upon previous animal-related work, we demonstrate that sera, polyclonal antibody fractions, and OSP-specific monoclonal antibodies recovered from humans surviving cholera block V. cholerae motility at both subagglutinating and agglutinating concentrations. This antimotility effect is reversed by preadsorbing sera and polyclonal antibody fractions with purified OSP and is associated with OSP-specific but not flagellin-specific monoclonal antibodies. Fab fragments of OSP-specific polyclonal antibodies do not inhibit motility, suggesting a requirement for antibody-mediated cross-linking in motility inhibition. We show that OSP-specific antibodies do not directly affect V. cholerae viability, but that OSP-specific monoclonal antibody highly protects against death in the murine cholera model. We used in vivo competitive index studies to demonstrate that OSP-specific antibodies impede colonization and survival of V. cholerae in intestinal tissues and that this impact is motility dependent. Our findings suggest that the impedance of motility by antibodies targeting V. cholerae OSP contributes to protection against cholera. IMPORTANCE Cholera is a severe dehydrating illness of humans caused by Vibrio cholerae. V. cholerae is a highly motile bacterium that has a single flagellum covered in lipopolysaccharide (LPS) displaying O-specific polysaccharide (OSP), and V. cholerae motility correlates with its ability to cause disease. The mechanisms of protection against cholera are not well understood; however, since V. cholerae is a noninvasive intestinal pathogen, it is likely that antibodies that bind the pathogen or its products in the intestinal lumen contribute to protection from infection. Here, we demonstrate that OSP-specific antibodies isolated from humans surviving cholera in Bangladesh inhibit V. cholerae motility and are associated with protection against challenge in a motility-dependent manner. |
| first_indexed | 2024-12-20T23:36:02Z |
| format | Article |
| id | doaj.art-d099d08206104bbf8c76536df01b508a |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-20T23:36:02Z |
| publishDate | 2020-12-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-d099d08206104bbf8c76536df01b508a2022-12-21T19:23:12ZengAmerican Society for MicrobiologymBio2150-75112020-12-0111610.1128/mBio.02847-20Humans Surviving Cholera Develop Antibodies against <named-content content-type="genus-species">Vibrio cholerae</named-content> O-Specific Polysaccharide That Inhibit Pathogen MotilityRichelle C. Charles0Meagan Kelly1Jenny M. Tam2Aklima Akter3Motaher Hossain4Kamrul Islam5Rajib Biswas6Mohammad Kamruzzaman7Fahima Chowdhury8Ashraful I. Khan9Daniel T. Leung10Ana Weil11Regina C. LaRocque12Taufiqur Rahman Bhuiyan13Atiqur Rahman14Leslie M. Mayo-Smith15Rachel L. Becker16Jatin M. Vyas17Christina S. Faherty18Kourtney P. Nickerson19Samantha Giffen20Alaina S. Ritter21Matthew K. Waldor22Peng Xu23Pavol Kováč24Stephen B. Calderwood25Robert C. Kauffman26Jens Wrammert27Firdausi Qadri28Jason B. Harris29Edward T. Ryan30Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USADivision of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USADivision of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USADivision of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USADivision of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USADivision of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USADivision of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USADivision of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USAInternational Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, BangladeshInternational Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, BangladeshDivision of Infectious Diseases, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USADivision of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USADivision of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USAInternational Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, BangladeshInternational Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, BangladeshDivision of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USADivision of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USADivision of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USADepartment of Pediatrics, MassGeneral Hospital for Children, Boston, Massachusetts, USADepartment of Pediatrics, MassGeneral Hospital for Children, Boston, Massachusetts, USADepartment of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USADivision of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USADepartment of Microbiology, Harvard Medical School, Boston, Massachusetts, USANIDDK, LBC, National Institutes of Health, Bethesda, Maryland, USANIDDK, LBC, National Institutes of Health, Bethesda, Maryland, USADivision of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USADivision of Infectious Disease, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USADivision of Infectious Disease, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USAInternational Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, BangladeshDivision of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USADivision of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USAABSTRACT The mechanism of protection against cholera afforded by previous illness or vaccination is currently unknown. We have recently shown that antibodies targeting O-specific polysaccharide (OSP) of Vibrio cholerae correlate highly with protection against cholera. V. cholerae is highly motile and possesses a flagellum sheathed in OSP, and motility of V. cholerae correlates with virulence. Using high-speed video microscopy and building upon previous animal-related work, we demonstrate that sera, polyclonal antibody fractions, and OSP-specific monoclonal antibodies recovered from humans surviving cholera block V. cholerae motility at both subagglutinating and agglutinating concentrations. This antimotility effect is reversed by preadsorbing sera and polyclonal antibody fractions with purified OSP and is associated with OSP-specific but not flagellin-specific monoclonal antibodies. Fab fragments of OSP-specific polyclonal antibodies do not inhibit motility, suggesting a requirement for antibody-mediated cross-linking in motility inhibition. We show that OSP-specific antibodies do not directly affect V. cholerae viability, but that OSP-specific monoclonal antibody highly protects against death in the murine cholera model. We used in vivo competitive index studies to demonstrate that OSP-specific antibodies impede colonization and survival of V. cholerae in intestinal tissues and that this impact is motility dependent. Our findings suggest that the impedance of motility by antibodies targeting V. cholerae OSP contributes to protection against cholera. IMPORTANCE Cholera is a severe dehydrating illness of humans caused by Vibrio cholerae. V. cholerae is a highly motile bacterium that has a single flagellum covered in lipopolysaccharide (LPS) displaying O-specific polysaccharide (OSP), and V. cholerae motility correlates with its ability to cause disease. The mechanisms of protection against cholera are not well understood; however, since V. cholerae is a noninvasive intestinal pathogen, it is likely that antibodies that bind the pathogen or its products in the intestinal lumen contribute to protection from infection. Here, we demonstrate that OSP-specific antibodies isolated from humans surviving cholera in Bangladesh inhibit V. cholerae motility and are associated with protection against challenge in a motility-dependent manner.https://journals.asm.org/doi/10.1128/mBio.02847-20Vibrio choleraecholerahumanmotilitypathogenesis |
| spellingShingle | Richelle C. Charles Meagan Kelly Jenny M. Tam Aklima Akter Motaher Hossain Kamrul Islam Rajib Biswas Mohammad Kamruzzaman Fahima Chowdhury Ashraful I. Khan Daniel T. Leung Ana Weil Regina C. LaRocque Taufiqur Rahman Bhuiyan Atiqur Rahman Leslie M. Mayo-Smith Rachel L. Becker Jatin M. Vyas Christina S. Faherty Kourtney P. Nickerson Samantha Giffen Alaina S. Ritter Matthew K. Waldor Peng Xu Pavol Kováč Stephen B. Calderwood Robert C. Kauffman Jens Wrammert Firdausi Qadri Jason B. Harris Edward T. Ryan Humans Surviving Cholera Develop Antibodies against <named-content content-type="genus-species">Vibrio cholerae</named-content> O-Specific Polysaccharide That Inhibit Pathogen Motility mBio Vibrio cholerae cholera human motility pathogenesis |
| title | Humans Surviving Cholera Develop Antibodies against <named-content content-type="genus-species">Vibrio cholerae</named-content> O-Specific Polysaccharide That Inhibit Pathogen Motility |
| title_full | Humans Surviving Cholera Develop Antibodies against <named-content content-type="genus-species">Vibrio cholerae</named-content> O-Specific Polysaccharide That Inhibit Pathogen Motility |
| title_fullStr | Humans Surviving Cholera Develop Antibodies against <named-content content-type="genus-species">Vibrio cholerae</named-content> O-Specific Polysaccharide That Inhibit Pathogen Motility |
| title_full_unstemmed | Humans Surviving Cholera Develop Antibodies against <named-content content-type="genus-species">Vibrio cholerae</named-content> O-Specific Polysaccharide That Inhibit Pathogen Motility |
| title_short | Humans Surviving Cholera Develop Antibodies against <named-content content-type="genus-species">Vibrio cholerae</named-content> O-Specific Polysaccharide That Inhibit Pathogen Motility |
| title_sort | humans surviving cholera develop antibodies against named content content type genus species vibrio cholerae named content o specific polysaccharide that inhibit pathogen motility |
| topic | Vibrio cholerae cholera human motility pathogenesis |
| url | https://journals.asm.org/doi/10.1128/mBio.02847-20 |
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