Humans Surviving Cholera Develop Antibodies against Vibrio cholerae O-Specific Polysaccharide That Inhibit Pathogen Motility

mBio

Samantha Giffen¹  Matthew K. Waldor²  Christina S. Faherty³  Kourtney P. Nickerson³  Jens Wrammert⁴  Robert C. Kauffman⁴  Daniel T. Leung⁵  Jason B. Harris⁶  Rajib Biswas⁶  Alaina S. Ritter⁶  Aklima Akter⁶  Jatin M. Vyas⁶  Richelle C. Charles⁶  Stephen B. Calderwood⁶  Ana Weil⁶  Rachel L. Becker⁶  Jenny M. Tam⁶  Motaher Hossain⁶  Kamrul Islam⁶  Edward T. Ryan⁶  Regina C. LaRocque⁶  Meagan Kelly⁶  Leslie M. Mayo-Smith⁶  Mohammad Kamruzzaman⁶  Fahima Chowdhury⁷  Firdausi Qadri⁷  Ashraful I. Khan⁷  Atiqur Rahman⁷  Taufiqur Rahman Bhuiyan⁷  Peng Xu⁸  Pavol Kováč⁸ 

[1] Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA;Department of Microbiology, Harvard Medical School, Boston, Massachusetts, USA;Department of Pediatrics, MassGeneral Hospital for Children, Boston, Massachusetts, USA;Division of Infectious Disease, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA;Division of Infectious Diseases, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA;Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA;International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh;NIDDK, LBC, National Institutes of Health, Bethesda, Maryland, USA;

关键词: Vibrio cholerae;    cholera;    human;    motility;    pathogenesis;   

DOI  :  10.1128/mBio.02847-20

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown