The microbiota metabolite indole inhibits Salmonella virulence: Involvement of the PhoPQ two-component system.
The microbial community present in the gastrointestinal tract is an important component of the host defense against pathogen infections. We previously demonstrated that indole, a microbial metabolite of tryptophan, reduces enterohemorrhagic Escherichia coli O157:H7 attachment to intestinal epithelia...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5771565?pdf=render |
| _version_ | 1819108345688096768 |
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| author | Nandita Kohli Zeni Crisp Rebekah Riordan Michael Li Robert C Alaniz Arul Jayaraman |
| author_facet | Nandita Kohli Zeni Crisp Rebekah Riordan Michael Li Robert C Alaniz Arul Jayaraman |
| author_sort | Nandita Kohli |
| collection | DOAJ |
| description | The microbial community present in the gastrointestinal tract is an important component of the host defense against pathogen infections. We previously demonstrated that indole, a microbial metabolite of tryptophan, reduces enterohemorrhagic Escherichia coli O157:H7 attachment to intestinal epithelial cells and biofilm formation, suggesting that indole may be an effector/attenuator of colonization for a number of enteric pathogens. Here, we report that indole attenuates Salmonella Typhimurium (Salmonella) virulence and invasion as well as increases resistance to colonization in host cells. Indole-exposed Salmonella colonized mice less effectively compared to solvent-treated controls, as evident by competitive index values less than 1 in multiple organs. Indole-exposed Salmonella demonstrated 160-fold less invasion of HeLa epithelial cells and 2-fold less invasion of J774A.1 macrophages compared to solvent-treated controls. However, indole did not affect Salmonella intracellular survival in J774A.1 macrophages suggesting that indole primarily affects Salmonella invasion. The decrease in invasion was corroborated by a decrease in expression of multiple Salmonella Pathogenicity Island-1 (SPI-1) genes. We also identified that the effect of indole was mediated by both PhoPQ-dependent and independent mechanisms. Indole also synergistically enhanced the inhibitory effect of a short chain fatty acid cocktail on SPI-1 gene expression. Lastly, indole-treated HeLa cells were 70% more resistant to Salmonella invasion suggesting that indole also increases resistance of epithelial cells to colonization. Our results demonstrate that indole is an important microbiota metabolite that has direct anti-infective effects on Salmonella and host cells, revealing novel mechanisms of pathogen colonization resistance. |
| first_indexed | 2024-12-22T03:08:28Z |
| format | Article |
| id | doaj.art-575d3666b0364c74b321ff6108861cf4 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T03:08:28Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-575d3666b0364c74b321ff6108861cf42022-12-21T18:40:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01131e019061310.1371/journal.pone.0190613The microbiota metabolite indole inhibits Salmonella virulence: Involvement of the PhoPQ two-component system.Nandita KohliZeni CrispRebekah RiordanMichael LiRobert C AlanizArul JayaramanThe microbial community present in the gastrointestinal tract is an important component of the host defense against pathogen infections. We previously demonstrated that indole, a microbial metabolite of tryptophan, reduces enterohemorrhagic Escherichia coli O157:H7 attachment to intestinal epithelial cells and biofilm formation, suggesting that indole may be an effector/attenuator of colonization for a number of enteric pathogens. Here, we report that indole attenuates Salmonella Typhimurium (Salmonella) virulence and invasion as well as increases resistance to colonization in host cells. Indole-exposed Salmonella colonized mice less effectively compared to solvent-treated controls, as evident by competitive index values less than 1 in multiple organs. Indole-exposed Salmonella demonstrated 160-fold less invasion of HeLa epithelial cells and 2-fold less invasion of J774A.1 macrophages compared to solvent-treated controls. However, indole did not affect Salmonella intracellular survival in J774A.1 macrophages suggesting that indole primarily affects Salmonella invasion. The decrease in invasion was corroborated by a decrease in expression of multiple Salmonella Pathogenicity Island-1 (SPI-1) genes. We also identified that the effect of indole was mediated by both PhoPQ-dependent and independent mechanisms. Indole also synergistically enhanced the inhibitory effect of a short chain fatty acid cocktail on SPI-1 gene expression. Lastly, indole-treated HeLa cells were 70% more resistant to Salmonella invasion suggesting that indole also increases resistance of epithelial cells to colonization. Our results demonstrate that indole is an important microbiota metabolite that has direct anti-infective effects on Salmonella and host cells, revealing novel mechanisms of pathogen colonization resistance.http://europepmc.org/articles/PMC5771565?pdf=render |
| spellingShingle | Nandita Kohli Zeni Crisp Rebekah Riordan Michael Li Robert C Alaniz Arul Jayaraman The microbiota metabolite indole inhibits Salmonella virulence: Involvement of the PhoPQ two-component system. PLoS ONE |
| title | The microbiota metabolite indole inhibits Salmonella virulence: Involvement of the PhoPQ two-component system. |
| title_full | The microbiota metabolite indole inhibits Salmonella virulence: Involvement of the PhoPQ two-component system. |
| title_fullStr | The microbiota metabolite indole inhibits Salmonella virulence: Involvement of the PhoPQ two-component system. |
| title_full_unstemmed | The microbiota metabolite indole inhibits Salmonella virulence: Involvement of the PhoPQ two-component system. |
| title_short | The microbiota metabolite indole inhibits Salmonella virulence: Involvement of the PhoPQ two-component system. |
| title_sort | microbiota metabolite indole inhibits salmonella virulence involvement of the phopq two component system |
| url | http://europepmc.org/articles/PMC5771565?pdf=render |
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