Host-derived O-glycans inhibit toxigenic conversion by a virulence-encoding phage in Vibrio cholerae
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. Despi...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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EMBO
2023
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| Online Access: | https://hdl.handle.net/1721.1/147918 |
| _version_ | 1811090229989212160 |
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| author | Wang, Benjamin X Takagi, Julie McShane, Abigail Park, Jin Hwan Aoki, Kazuhiro Griffin, Catherine Teschler, Jennifer Kitts, Giordan Minzer, Giulietta Tiemeyer, Michael Hevey, Rachel Yildiz, Fitnat Ribbeck, Katharina |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Wang, Benjamin X Takagi, Julie McShane, Abigail Park, Jin Hwan Aoki, Kazuhiro Griffin, Catherine Teschler, Jennifer Kitts, Giordan Minzer, Giulietta Tiemeyer, Michael Hevey, Rachel Yildiz, Fitnat Ribbeck, Katharina |
| author_sort | Wang, Benjamin X |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T14:39:11Z |
| format | Article |
| id | mit-1721.1/147918 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T14:39:11Z |
| publishDate | 2023 |
| publisher | EMBO |
| record_format | dspace |
| spelling | mit-1721.1/1479182023-02-07T03:14:50Z Host-derived O-glycans inhibit toxigenic conversion by a virulence-encoding phage in Vibrio cholerae Wang, Benjamin X Takagi, Julie McShane, Abigail Park, Jin Hwan Aoki, Kazuhiro Griffin, Catherine Teschler, Jennifer Kitts, Giordan Minzer, Giulietta Tiemeyer, Michael Hevey, Rachel Yildiz, Fitnat Ribbeck, Katharina Massachusetts Institute of Technology. Department of Biological Engineering 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. 2023-02-06T19:20:23Z 2023-02-06T19:20:23Z 2022-12-12 2023-02-06T19:16:02Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/147918 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. en 10.15252/embj.2022111562 The EMBO Journal Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf EMBO EMBO Press |
| spellingShingle | Wang, Benjamin X Takagi, Julie McShane, Abigail Park, Jin Hwan Aoki, Kazuhiro Griffin, Catherine Teschler, Jennifer Kitts, Giordan Minzer, Giulietta Tiemeyer, Michael Hevey, Rachel Yildiz, Fitnat Ribbeck, Katharina Host-derived O-glycans inhibit toxigenic conversion by a virulence-encoding phage in Vibrio cholerae |
| title | Host-derived O-glycans inhibit toxigenic conversion by a virulence-encoding phage in Vibrio cholerae |
| title_full | Host-derived O-glycans inhibit toxigenic conversion by a virulence-encoding phage in Vibrio cholerae |
| title_fullStr | Host-derived O-glycans inhibit toxigenic conversion by a virulence-encoding phage in Vibrio cholerae |
| title_full_unstemmed | Host-derived O-glycans inhibit toxigenic conversion by a virulence-encoding phage in Vibrio cholerae |
| title_short | Host-derived O-glycans inhibit toxigenic conversion by a virulence-encoding phage in Vibrio cholerae |
| title_sort | host derived o glycans inhibit toxigenic conversion by a virulence encoding phage in vibrio cholerae |
| url | https://hdl.handle.net/1721.1/147918 |
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