Journal Article

Human antibody targeting Vibrio cholerae O1 O-specific polysaccharide induces an amotile hypovirulent bacterial phenotype: mechanism of protection against cholera

Xu, Peng, Kováč, Pavol, Faherty, Christina S., Harris, Jason B., Waldor, Matthew K., Senger, Stefania, Sadreyev, Ruslan I., Khan, Ashraful Islam, Verma, Smriti, Asp, Merrill, Calderwood, Stephen B., Qadri, Firdausi, Ryan, Edward T., Cetinbas, Murat, Charles, Richelle C., Akter, Aklima, Tai, Jung-Shen Benny, Wrammert, Jens, Yan, Jing, Bhuiyan, Taufiqur Rahman, Chowdhury, Fahima, Kelly, Meagan, Janardhanan, Jeshina, Wagh, Chanchal R.

2025

Overview

Immunity to cholera is largely mediated by antibodies targeting the O-specific polysaccharide (OSP) of Vibrio cholerae, including through agglutination as well as inhibition of bacterial motility. Here, we used bacterial transcriptomic, biochemical, and cellular analyses to evaluate additional effects of OSP-specific antibodies on V. cholerae in complex media containing mucin and in a human enteroid-derived monolayer colonization model. We found that anti-OSP antibody in mucin impacts bacterial motility, growth, metabolic activity, extracellular matrix production, and levels of cyclic di-GMP. We did not observe a direct effect on bacterial viability, sodium motive force gradient, membrane integrity for large molecules, or virulence gene or regulon expression in bacterial cultures, although cholera toxin detection was significantly decreased in the enteroid model. Our results uncover the broad impact of anti-OSP antibodies in the presence of mucin on V. cholerae physiology and suggest several ways OSP-specific antibodies mediate protection against cholera in humans.

• Publisher: American Society for Microbiology,American Society for Microbiology (ASM)
• Subject: Agglutination / Animal Infection Models / anti-OSP antibody / Antibodies / Antibodies, Bacterial - immunology / Antibodies, Monoclonal - immunology / Antigen Diversity / Bacteria / Bacterial-Host Interactions / biofilm / Biofilms / Campylobacteriosis / Cell culture / Cellular stress response / Cholera / Cholera - immunology / Cholera - microbiology / Cholera - prevention & control / Cholera Immunity / Cholera toxin / Clinical Microbiology and Infectious Diseases / Extracellular matrix / Gene Expression Profiling / Gene Expression Regulation, Bacterial / Host-Pathogen Interactions / Humans / Infant Mouse Cholera Model / Intermediates / Locomotion / Metabolism / Microbial Pathogenesis and Immunology / Monoclonal antibodies / Motility / Mucin / Mucins / Mucosal Antibodies (e.g., IgA) / Mucosal Immunity / O Antigens - immunology / Pathogen-Specific Immunity / Pathogenesis and Host Response / Phenotype / Phenotypes / Pneumocystis Infection / Polysaccharide Antigens / Polysaccharides / Research Article / RNA polymerase / Salmonella / Small intestine / Toxins / transcriptomic profiling / Transcriptomics / Vibrio cholerae / Vibrio cholerae O1 - drug effects / Vibrio cholerae O1 - genetics / Vibrio cholerae O1 - immunology / Vibrio cholerae O1 - pathogenicity / Vibrio cholerae O1 - physiology / Virulence