Host-derived O-glycans inhibit toxigenic conversion by a virulence-encoding phage in Vibrio cholerae. EMBO J 2023 Feb 01;42(3):e111562
Date
12/13/2022Pubmed ID
36504455Pubmed Central ID
PMC9890226DOI
10.15252/embj.2022111562Scopus ID
2-s2.0-85143780784 (requires institutional sign-in at Scopus site) 21 CitationsAbstract
Pandemic and endemic strains of Vibrio cholerae arise from toxigenic conversion by the CTXφ bacteriophage, a process by which CTXφ infects nontoxigenic strains of V. cholerae. CTXφ encodes the cholera toxin, an enterotoxin responsible for the watery diarrhea associated with cholera infections. Despite the critical role of CTXφ during infections, signals that affect CTXφ-driven toxigenic conversion or expression of the CTXφ-encoded cholera toxin remain poorly characterized, particularly in the context of the gut mucosa. Here, we identify mucin polymers as potent regulators of CTXφ-driven pathogenicity in V. cholerae. Our results indicate that mucin-associated O-glycans block toxigenic conversion by CTXφ and suppress the expression of CTXφ-related virulence factors, including the toxin co-regulated pilus and cholera toxin, by interfering with the TcpP/ToxR/ToxT virulence pathway. By synthesizing individual mucin glycan structures de novo, we identify the Core 2 motif as the critical structure governing this virulence attenuation. Overall, our results highlight a novel mechanism by which mucins and their associated O-glycan structures affect CTXφ-mediated evolution and pathogenicity of V. cholerae, underscoring the potential regulatory power housed within mucus.
Author List
Wang BX, Takagi J, McShane A, Park JH, Aoki K, Griffin C, Teschler J, Kitts G, Minzer G, Tiemeyer M, Hevey R, Yildiz F, Ribbeck KAuthor
Kazuhiro Aoki PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
BacteriophagesCholera Toxin
Mucins
Polysaccharides
Vibrio cholerae
Virulence
