title: Vibrio cholerae virulence regulator-coordinated evasion of host immunity.
abstract: To successfully propagate and cause disease, pathogenic bacteria must modulate their transcriptional activities in response to pressures exerted by the host immune system, including secreted immunoglobulins such as secretory IgA (S-IgA), which can bind and agglutinate bacteria. Here, we present a previously undescribed flow cytometry-based screening method to identify bacterial genes expressed in vitro and repressed during infections of Vibrio cholerae, an aquatic Gram-negative bacterium responsible for the severe diarrheal disease cholera. We identified a type IV mannose-sensitive hemagglutinin (MSHA) pilus that is repressed specifically in vivo. We showed that bacteria that failed to turn off MSHA biosynthesis were unable to colonize the intestines of infant mice in the presence of S-IgA. We also found that V. cholerae bound S-IgA in an MSHA-dependent and mannose-sensitive fashion and that binding of S-IgA prevented bacteria from penetrating mucus barriers and attaching to the surface of epithelial cells. The ability of V. cholerae to evade the non-antigen-specific binding of S-IgA by down-regulating a surface adhesin represents a previously undescribed mechanism of immune evasion in pathogenic bacteria. In addition, we found that repression of MSHA was mediated by the key virulence transcription factor ToxT, indicating that V. cholerae is able to coordinate both virulence gene activation and repression to evade host defenses and successfully colonize intestines.
authors.affiliation: Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Ansel
authors.initials: A
authors.lastname: Hsiao
authors.forename: Zhi
authors.initials: Z
authors.lastname: Liu
authors.forename: Adam
authors.initials: A
authors.lastname: Joelsson
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000382:microbiology; D036781:Fimbriae Proteins / Q000096:biosynthesis / Q000235:genetics; D010861:Fimbriae, Bacterial / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial / Q000235:genetics; D006801:Humans; D007109:Immunity / Q000276:immunology*; D007071:Immunoglobulin A, Secretory / Q000276:immunology; D037601:Mannose-Binding Lectin / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D014734:Vibrio cholerae / Q000166:cytology / Q000472:pathogenicity* / Q000502:physiology; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D007071:Immunoglobulin A, Secretory; D037601:Mannose-Binding Lectin; C101032:MshA protein, Vibrio cholerae; D012333:RNA, Messenger; D014157:Transcription Factors; D036781:Fimbriae Proteins; C075626:tcpN protein, Vibrio cholerae