Host‐derived O‐glycans inhibit toxigenic conversion by a virulence‐encoding phage in Vibrio cholerae
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Dec 12, 2022
- Source ID
- 10.15252/embj.2022111562
Entities
People
- Abigail Mcshane
- Benjamin Wang
- Catherine Griffin
- Fitnat Yildiz
- Giordan Kitts
- Giulietta Minzer
- Jennifer Teschler
- Jin Hwan Park
- Julie Takagi
- Katharina Ribbeck
- Kazuhiro Aoki
- Michael Tiemeyer
- Rachel Hevey
Organizations
- Army Research Office
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases
- Massachusetts Institute of Technology
- National Institute of Allergy and Infectious Diseases
- National Institute of Biomedical Imaging and Bioengineering
- National Institute of Environmental Health Sciences
- National Science Foundation
- Stanford University
- Swiss National Science Foundation
- University of Basel
- University of Georgia