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Recombinant production of a diffusible signal factor inhibits Salmonella invasion and animal carriage

The complex chemical environment of the intestine is defined largely by the metabolic products of the resident microbiota. Enteric pathogens, elegantly evolved to thrive in the gut, use these chemical products as signals to recognize specific niches and to promote their survival and virulence. Our p...

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Autores principales: Rather, Mudasir Ali, Chowdhury, Rimi, Pavinski Bitar, Paulina D., Altier, Craig
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10171134/
https://www.ncbi.nlm.nih.gov/pubmed/37158497
http://dx.doi.org/10.1080/19490976.2023.2208498
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author Rather, Mudasir Ali
Chowdhury, Rimi
Pavinski Bitar, Paulina D.
Altier, Craig
author_facet Rather, Mudasir Ali
Chowdhury, Rimi
Pavinski Bitar, Paulina D.
Altier, Craig
author_sort Rather, Mudasir Ali
collection PubMed
description The complex chemical environment of the intestine is defined largely by the metabolic products of the resident microbiota. Enteric pathogens, elegantly evolved to thrive in the gut, use these chemical products as signals to recognize specific niches and to promote their survival and virulence. Our previous work has shown that a specific class of quorum-sensing molecules found within the gut, termed diffusible signal factors (DSF), signals the repression of Salmonella tissue invasion, thus defining a means by which this pathogen recognizes its location and modulates virulence to optimize its survival. Here, we determined whether the recombinant production of a DSF could reduce Salmonella virulence in vitro and in vivo. We found that the most potent repressor of Salmonella invasion, cis-2-hexadecenoic acid (c2-HDA), could be recombinantly produced in E. coli by the addition of a single exogenous gene encoding a fatty acid enoyl-CoA dehydratase/thioesterase and that co-culture of the recombinant strain with Salmonella potently inhibited tissue invasion by repressing Salmonella genes required for this essential virulence function. Using the well characterized E. coli Nissle 1917 strain and a chicken infection model, we found that the recombinant DSF-producing strain could be stably maintained in the large intestine. Further, challenge studies demonstrated that this recombinant organism could significantly reduce Salmonella colonization of the cecum, the site of carriage in this animal species. These findings thus describe a plausible means by which Salmonella virulence may be affected in animals by in situ chemical manipulation of functions essential for colonization and virulence.
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spelling pubmed-101711342023-05-11 Recombinant production of a diffusible signal factor inhibits Salmonella invasion and animal carriage Rather, Mudasir Ali Chowdhury, Rimi Pavinski Bitar, Paulina D. Altier, Craig Gut Microbes Research Paper The complex chemical environment of the intestine is defined largely by the metabolic products of the resident microbiota. Enteric pathogens, elegantly evolved to thrive in the gut, use these chemical products as signals to recognize specific niches and to promote their survival and virulence. Our previous work has shown that a specific class of quorum-sensing molecules found within the gut, termed diffusible signal factors (DSF), signals the repression of Salmonella tissue invasion, thus defining a means by which this pathogen recognizes its location and modulates virulence to optimize its survival. Here, we determined whether the recombinant production of a DSF could reduce Salmonella virulence in vitro and in vivo. We found that the most potent repressor of Salmonella invasion, cis-2-hexadecenoic acid (c2-HDA), could be recombinantly produced in E. coli by the addition of a single exogenous gene encoding a fatty acid enoyl-CoA dehydratase/thioesterase and that co-culture of the recombinant strain with Salmonella potently inhibited tissue invasion by repressing Salmonella genes required for this essential virulence function. Using the well characterized E. coli Nissle 1917 strain and a chicken infection model, we found that the recombinant DSF-producing strain could be stably maintained in the large intestine. Further, challenge studies demonstrated that this recombinant organism could significantly reduce Salmonella colonization of the cecum, the site of carriage in this animal species. These findings thus describe a plausible means by which Salmonella virulence may be affected in animals by in situ chemical manipulation of functions essential for colonization and virulence. Taylor & Francis 2023-05-09 /pmc/articles/PMC10171134/ /pubmed/37158497 http://dx.doi.org/10.1080/19490976.2023.2208498 Text en © 2023 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
spellingShingle Research Paper
Rather, Mudasir Ali
Chowdhury, Rimi
Pavinski Bitar, Paulina D.
Altier, Craig
Recombinant production of a diffusible signal factor inhibits Salmonella invasion and animal carriage
title Recombinant production of a diffusible signal factor inhibits Salmonella invasion and animal carriage
title_full Recombinant production of a diffusible signal factor inhibits Salmonella invasion and animal carriage
title_fullStr Recombinant production of a diffusible signal factor inhibits Salmonella invasion and animal carriage
title_full_unstemmed Recombinant production of a diffusible signal factor inhibits Salmonella invasion and animal carriage
title_short Recombinant production of a diffusible signal factor inhibits Salmonella invasion and animal carriage
title_sort recombinant production of a diffusible signal factor inhibits salmonella invasion and animal carriage
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10171134/
https://www.ncbi.nlm.nih.gov/pubmed/37158497
http://dx.doi.org/10.1080/19490976.2023.2208498
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