Cargando…
Humans Surviving Cholera Develop Antibodies against Vibrio cholerae O-Specific Polysaccharide That Inhibit Pathogen Motility
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 possess...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683404/ https://www.ncbi.nlm.nih.gov/pubmed/33203761 http://dx.doi.org/10.1128/mBio.02847-20 |
_version_ | 1783612869557878784 |
---|---|
author | Charles, Richelle C. Kelly, Meagan Tam, Jenny M. Akter, Aklima Hossain, Motaher Islam, Kamrul Biswas, Rajib Kamruzzaman, Mohammad Chowdhury, Fahima Khan, Ashraful I. Leung, Daniel T. Weil, Ana LaRocque, Regina C. Bhuiyan, Taufiqur Rahman Rahman, Atiqur Mayo-Smith, Leslie M. Becker, Rachel L. Vyas, Jatin M. Faherty, Christina S. Nickerson, Kourtney P. Giffen, Samantha Ritter, Alaina S. Waldor, Matthew K. Xu, Peng Kováč, Pavol Calderwood, Stephen B. Kauffman, Robert C. Wrammert, Jens Qadri, Firdausi Harris, Jason B. Ryan, Edward T. |
author_facet | Charles, Richelle C. Kelly, Meagan Tam, Jenny M. Akter, Aklima Hossain, Motaher Islam, Kamrul Biswas, Rajib Kamruzzaman, Mohammad Chowdhury, Fahima Khan, Ashraful I. Leung, Daniel T. Weil, Ana LaRocque, Regina C. Bhuiyan, Taufiqur Rahman Rahman, Atiqur Mayo-Smith, Leslie M. Becker, Rachel L. Vyas, Jatin M. Faherty, Christina S. Nickerson, Kourtney P. Giffen, Samantha Ritter, Alaina S. Waldor, Matthew K. Xu, Peng Kováč, Pavol Calderwood, Stephen B. Kauffman, Robert C. Wrammert, Jens Qadri, Firdausi Harris, Jason B. Ryan, Edward T. |
author_sort | Charles, Richelle C. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7683404 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-76834042020-11-30 Humans Surviving Cholera Develop Antibodies against Vibrio cholerae O-Specific Polysaccharide That Inhibit Pathogen Motility Charles, Richelle C. Kelly, Meagan Tam, Jenny M. Akter, Aklima Hossain, Motaher Islam, Kamrul Biswas, Rajib Kamruzzaman, Mohammad Chowdhury, Fahima Khan, Ashraful I. Leung, Daniel T. Weil, Ana LaRocque, Regina C. Bhuiyan, Taufiqur Rahman Rahman, Atiqur Mayo-Smith, Leslie M. Becker, Rachel L. Vyas, Jatin M. Faherty, Christina S. Nickerson, Kourtney P. Giffen, Samantha Ritter, Alaina S. Waldor, Matthew K. Xu, Peng Kováč, Pavol Calderwood, Stephen B. Kauffman, Robert C. Wrammert, Jens Qadri, Firdausi Harris, Jason B. Ryan, Edward T. mBio Research Article 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. American Society for Microbiology 2020-11-17 /pmc/articles/PMC7683404/ /pubmed/33203761 http://dx.doi.org/10.1128/mBio.02847-20 Text en Copyright © 2020 Charles et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Charles, Richelle C. Kelly, Meagan Tam, Jenny M. Akter, Aklima Hossain, Motaher Islam, Kamrul Biswas, Rajib Kamruzzaman, Mohammad Chowdhury, Fahima Khan, Ashraful I. Leung, Daniel T. Weil, Ana LaRocque, Regina C. Bhuiyan, Taufiqur Rahman Rahman, Atiqur Mayo-Smith, Leslie M. Becker, Rachel L. Vyas, Jatin M. Faherty, Christina S. Nickerson, Kourtney P. Giffen, Samantha Ritter, Alaina S. Waldor, Matthew K. Xu, Peng Kováč, Pavol Calderwood, Stephen B. Kauffman, Robert C. Wrammert, Jens Qadri, Firdausi Harris, Jason B. Ryan, Edward T. Humans Surviving Cholera Develop Antibodies against Vibrio cholerae O-Specific Polysaccharide That Inhibit Pathogen Motility |
title | Humans Surviving Cholera Develop Antibodies against Vibrio cholerae O-Specific Polysaccharide That Inhibit Pathogen Motility |
title_full | Humans Surviving Cholera Develop Antibodies against Vibrio cholerae O-Specific Polysaccharide That Inhibit Pathogen Motility |
title_fullStr | Humans Surviving Cholera Develop Antibodies against Vibrio cholerae O-Specific Polysaccharide That Inhibit Pathogen Motility |
title_full_unstemmed | Humans Surviving Cholera Develop Antibodies against Vibrio cholerae O-Specific Polysaccharide That Inhibit Pathogen Motility |
title_short | Humans Surviving Cholera Develop Antibodies against Vibrio cholerae O-Specific Polysaccharide That Inhibit Pathogen Motility |
title_sort | humans surviving cholera develop antibodies against vibrio cholerae o-specific polysaccharide that inhibit pathogen motility |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683404/ https://www.ncbi.nlm.nih.gov/pubmed/33203761 http://dx.doi.org/10.1128/mBio.02847-20 |
work_keys_str_mv | AT charlesrichellec humanssurvivingcholeradevelopantibodiesagainstvibriocholeraeospecificpolysaccharidethatinhibitpathogenmotility AT kellymeagan humanssurvivingcholeradevelopantibodiesagainstvibriocholeraeospecificpolysaccharidethatinhibitpathogenmotility AT tamjennym humanssurvivingcholeradevelopantibodiesagainstvibriocholeraeospecificpolysaccharidethatinhibitpathogenmotility AT akteraklima humanssurvivingcholeradevelopantibodiesagainstvibriocholeraeospecificpolysaccharidethatinhibitpathogenmotility AT hossainmotaher humanssurvivingcholeradevelopantibodiesagainstvibriocholeraeospecificpolysaccharidethatinhibitpathogenmotility AT islamkamrul humanssurvivingcholeradevelopantibodiesagainstvibriocholeraeospecificpolysaccharidethatinhibitpathogenmotility AT biswasrajib humanssurvivingcholeradevelopantibodiesagainstvibriocholeraeospecificpolysaccharidethatinhibitpathogenmotility AT kamruzzamanmohammad humanssurvivingcholeradevelopantibodiesagainstvibriocholeraeospecificpolysaccharidethatinhibitpathogenmotility AT chowdhuryfahima humanssurvivingcholeradevelopantibodiesagainstvibriocholeraeospecificpolysaccharidethatinhibitpathogenmotility AT khanashrafuli humanssurvivingcholeradevelopantibodiesagainstvibriocholeraeospecificpolysaccharidethatinhibitpathogenmotility AT leungdanielt humanssurvivingcholeradevelopantibodiesagainstvibriocholeraeospecificpolysaccharidethatinhibitpathogenmotility AT weilana humanssurvivingcholeradevelopantibodiesagainstvibriocholeraeospecificpolysaccharidethatinhibitpathogenmotility AT larocquereginac humanssurvivingcholeradevelopantibodiesagainstvibriocholeraeospecificpolysaccharidethatinhibitpathogenmotility AT bhuiyantaufiqurrahman humanssurvivingcholeradevelopantibodiesagainstvibriocholeraeospecificpolysaccharidethatinhibitpathogenmotility AT rahmanatiqur humanssurvivingcholeradevelopantibodiesagainstvibriocholeraeospecificpolysaccharidethatinhibitpathogenmotility AT mayosmithlesliem humanssurvivingcholeradevelopantibodiesagainstvibriocholeraeospecificpolysaccharidethatinhibitpathogenmotility AT beckerrachell humanssurvivingcholeradevelopantibodiesagainstvibriocholeraeospecificpolysaccharidethatinhibitpathogenmotility AT vyasjatinm humanssurvivingcholeradevelopantibodiesagainstvibriocholeraeospecificpolysaccharidethatinhibitpathogenmotility AT fahertychristinas humanssurvivingcholeradevelopantibodiesagainstvibriocholeraeospecificpolysaccharidethatinhibitpathogenmotility AT nickersonkourtneyp humanssurvivingcholeradevelopantibodiesagainstvibriocholeraeospecificpolysaccharidethatinhibitpathogenmotility AT giffensamantha humanssurvivingcholeradevelopantibodiesagainstvibriocholeraeospecificpolysaccharidethatinhibitpathogenmotility AT ritteralainas humanssurvivingcholeradevelopantibodiesagainstvibriocholeraeospecificpolysaccharidethatinhibitpathogenmotility AT waldormatthewk humanssurvivingcholeradevelopantibodiesagainstvibriocholeraeospecificpolysaccharidethatinhibitpathogenmotility AT xupeng humanssurvivingcholeradevelopantibodiesagainstvibriocholeraeospecificpolysaccharidethatinhibitpathogenmotility AT kovacpavol humanssurvivingcholeradevelopantibodiesagainstvibriocholeraeospecificpolysaccharidethatinhibitpathogenmotility AT calderwoodstephenb humanssurvivingcholeradevelopantibodiesagainstvibriocholeraeospecificpolysaccharidethatinhibitpathogenmotility AT kauffmanrobertc humanssurvivingcholeradevelopantibodiesagainstvibriocholeraeospecificpolysaccharidethatinhibitpathogenmotility AT wrammertjens humanssurvivingcholeradevelopantibodiesagainstvibriocholeraeospecificpolysaccharidethatinhibitpathogenmotility AT qadrifirdausi humanssurvivingcholeradevelopantibodiesagainstvibriocholeraeospecificpolysaccharidethatinhibitpathogenmotility AT harrisjasonb humanssurvivingcholeradevelopantibodiesagainstvibriocholeraeospecificpolysaccharidethatinhibitpathogenmotility AT ryanedwardt humanssurvivingcholeradevelopantibodiesagainstvibriocholeraeospecificpolysaccharidethatinhibitpathogenmotility |