Host-derived O-glycans inhibit toxigenic conversion by a virulence-encoding phage in Vibrio cholerae
Name
The EMBO Journal - 2022 - Wang - Host‐derived O‐glycans inhibit toxigenic conversion by a virulence‐encoding phage in.pdf
Description
Published version
Size
944.99 KB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Wang, Benjamin X
Takagi, Julie
McShane, Abigail
Park, Jin Hwan
Aoki, Kazuhiro
Griffin, Catherine
Teschler, Jennifer
Kitts, Giordan
Minzer, Giulietta
Tiemeyer, Michael
Date Issued
December 12, 2022
Journal
The EMBO Journal
Publisher
EMBO
Citation
Wang, Benjamin X, Takagi, Julie, McShane, Abigail, Park, Jin Hwan, Aoki, Kazuhiro et al. 2022. "Host-derived O-glycans inhibit toxigenic conversion by a virulence-encoding phage in Vibrio cholerae." The EMBO Journal.
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.15252/embj.2022111562
