A diffusible signal factor of the intestine dictates Salmonella invasion through its direct control of the virulence activator HilD.
Successful intestinal infection by Salmonella requires optimized invasion of the gut epithelium, a function that is energetically costly. Salmonella have therefore evolved to intricately regulate the expression of their virulence determinants by utilizing specific environmental cues. Here we show th...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2021-02-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1009357 |
| _version_ | 1818588810295902208 |
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| author | Rimi Chowdhury Paulina D Pavinski Bitar Ivan Keresztes Anthony M Condo Craig Altier |
| author_facet | Rimi Chowdhury Paulina D Pavinski Bitar Ivan Keresztes Anthony M Condo Craig Altier |
| author_sort | Rimi Chowdhury |
| collection | DOAJ |
| description | Successful intestinal infection by Salmonella requires optimized invasion of the gut epithelium, a function that is energetically costly. Salmonella have therefore evolved to intricately regulate the expression of their virulence determinants by utilizing specific environmental cues. Here we show that a powerful repressor of Salmonella invasion, a cis-2 unsaturated long chain fatty acid, is present in the murine large intestine. Originally identified in Xylella fastidiosa as a diffusible signal factor for quorum sensing, this fatty acid directly interacts with HilD, the master transcriptional regulator of Salmonella, and prevents hilA activation, thus inhibiting Salmonella invasion. We further identify the fatty acid binding region of HilD and show it to be selective and biased in favour of signal factors with a cis-2 unsaturation over other intestinal fatty acids. Single mutation of specific HilD amino acids to alanine prevented fatty acid binding, thereby alleviating their repressive effect on invasion. Together, these results highlight an exceedingly sensitive mechanism used by Salmonella to colonize its host by detecting and exploiting specific molecules present within the complex intestinal environment. |
| first_indexed | 2024-12-16T09:30:40Z |
| format | Article |
| id | doaj.art-ffd869ad4dea4ae3ada868dac169674d |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-16T09:30:40Z |
| publishDate | 2021-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-ffd869ad4dea4ae3ada868dac169674d2022-12-21T22:36:32ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742021-02-01172e100935710.1371/journal.ppat.1009357A diffusible signal factor of the intestine dictates Salmonella invasion through its direct control of the virulence activator HilD.Rimi ChowdhuryPaulina D Pavinski BitarIvan KeresztesAnthony M CondoCraig AltierSuccessful intestinal infection by Salmonella requires optimized invasion of the gut epithelium, a function that is energetically costly. Salmonella have therefore evolved to intricately regulate the expression of their virulence determinants by utilizing specific environmental cues. Here we show that a powerful repressor of Salmonella invasion, a cis-2 unsaturated long chain fatty acid, is present in the murine large intestine. Originally identified in Xylella fastidiosa as a diffusible signal factor for quorum sensing, this fatty acid directly interacts with HilD, the master transcriptional regulator of Salmonella, and prevents hilA activation, thus inhibiting Salmonella invasion. We further identify the fatty acid binding region of HilD and show it to be selective and biased in favour of signal factors with a cis-2 unsaturation over other intestinal fatty acids. Single mutation of specific HilD amino acids to alanine prevented fatty acid binding, thereby alleviating their repressive effect on invasion. Together, these results highlight an exceedingly sensitive mechanism used by Salmonella to colonize its host by detecting and exploiting specific molecules present within the complex intestinal environment.https://doi.org/10.1371/journal.ppat.1009357 |
| spellingShingle | Rimi Chowdhury Paulina D Pavinski Bitar Ivan Keresztes Anthony M Condo Craig Altier A diffusible signal factor of the intestine dictates Salmonella invasion through its direct control of the virulence activator HilD. PLoS Pathogens |
| title | A diffusible signal factor of the intestine dictates Salmonella invasion through its direct control of the virulence activator HilD. |
| title_full | A diffusible signal factor of the intestine dictates Salmonella invasion through its direct control of the virulence activator HilD. |
| title_fullStr | A diffusible signal factor of the intestine dictates Salmonella invasion through its direct control of the virulence activator HilD. |
| title_full_unstemmed | A diffusible signal factor of the intestine dictates Salmonella invasion through its direct control of the virulence activator HilD. |
| title_short | A diffusible signal factor of the intestine dictates Salmonella invasion through its direct control of the virulence activator HilD. |
| title_sort | diffusible signal factor of the intestine dictates salmonella invasion through its direct control of the virulence activator hild |
| url | https://doi.org/10.1371/journal.ppat.1009357 |
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