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A Novel Two-Component Signaling System Facilitates Uropathogenic Escherichia coli's Ability to Exploit Abundant Host Metabolites

Two-component signaling systems (TCSs) are major mechanisms by which bacteria adapt to environmental conditions. It follows then that TCSs would play important roles in the adaptation of pathogenic bacteria to host environments. However, no pathogen-associated TCS has been identified in uropathogeni...

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Autores principales: Cai, Wentong, Wannemuehler, Yvonne, Dell'Anna, Giuseppe, Nicholson, Bryon, Barbieri, Nicolle L., Kariyawasam, Subhashinie, Feng, Yaping, Logue, Catherine M., Nolan, Lisa K., Li, Ganwu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3694859/
https://www.ncbi.nlm.nih.gov/pubmed/23825943
http://dx.doi.org/10.1371/journal.ppat.1003428
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author Cai, Wentong
Wannemuehler, Yvonne
Dell'Anna, Giuseppe
Nicholson, Bryon
Barbieri, Nicolle L.
Kariyawasam, Subhashinie
Feng, Yaping
Logue, Catherine M.
Nolan, Lisa K.
Li, Ganwu
author_facet Cai, Wentong
Wannemuehler, Yvonne
Dell'Anna, Giuseppe
Nicholson, Bryon
Barbieri, Nicolle L.
Kariyawasam, Subhashinie
Feng, Yaping
Logue, Catherine M.
Nolan, Lisa K.
Li, Ganwu
author_sort Cai, Wentong
collection PubMed
description Two-component signaling systems (TCSs) are major mechanisms by which bacteria adapt to environmental conditions. It follows then that TCSs would play important roles in the adaptation of pathogenic bacteria to host environments. However, no pathogen-associated TCS has been identified in uropathogenic Escherichia coli (UPEC). Here, we identified a novel TCS, which we termed KguS/KguR (KguS: α-ketoglutarate utilization sensor; KguR: α-ketoglutarate utilization regulator) in UPEC CFT073, a strain isolated from human pyelonephritis. kguS/kguR was strongly associated with UPEC but was found only rarely among other E. coli including commensal and intestinal pathogenic strains. An in vivo competition assay in a mouse UTI model showed that deletion of kguS/kguR in UPEC CFT073 resulted in a significant reduction in its colonization of the bladders and kidneys of mice, suggesting that KguS/KguR contributed to UPEC fitness in vivo. Comparative proteomics identified the target gene products of KguS/KguR, and sequence analysis showed that TCS KguS/KguR and its targeted-genes, c5032 to c5039, are encoded on a genomic island, which is not present in intestinal pathogenic E. coli. Expression of the target genes was induced by α-ketoglutarate (α-KG). These genes were further shown to be involved in utilization of α-KG as a sole carbon source under anaerobic conditions. KguS/KguR contributed to the regulation of the target genes with the direct regulation by KguR verified using an electrophoretic mobility shift assay. In addition, oxygen deficiency positively modulated expression of kguS/kguR and its target genes. Taken altogether, this study describes the first UPEC-associated TCS that functions in controlling the utilization of α-ketoglutarate in vivo thereby facilitating UPEC adaptation to life inside the urinary tract.
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spelling pubmed-36948592013-07-03 A Novel Two-Component Signaling System Facilitates Uropathogenic Escherichia coli's Ability to Exploit Abundant Host Metabolites Cai, Wentong Wannemuehler, Yvonne Dell'Anna, Giuseppe Nicholson, Bryon Barbieri, Nicolle L. Kariyawasam, Subhashinie Feng, Yaping Logue, Catherine M. Nolan, Lisa K. Li, Ganwu PLoS Pathog Research Article Two-component signaling systems (TCSs) are major mechanisms by which bacteria adapt to environmental conditions. It follows then that TCSs would play important roles in the adaptation of pathogenic bacteria to host environments. However, no pathogen-associated TCS has been identified in uropathogenic Escherichia coli (UPEC). Here, we identified a novel TCS, which we termed KguS/KguR (KguS: α-ketoglutarate utilization sensor; KguR: α-ketoglutarate utilization regulator) in UPEC CFT073, a strain isolated from human pyelonephritis. kguS/kguR was strongly associated with UPEC but was found only rarely among other E. coli including commensal and intestinal pathogenic strains. An in vivo competition assay in a mouse UTI model showed that deletion of kguS/kguR in UPEC CFT073 resulted in a significant reduction in its colonization of the bladders and kidneys of mice, suggesting that KguS/KguR contributed to UPEC fitness in vivo. Comparative proteomics identified the target gene products of KguS/KguR, and sequence analysis showed that TCS KguS/KguR and its targeted-genes, c5032 to c5039, are encoded on a genomic island, which is not present in intestinal pathogenic E. coli. Expression of the target genes was induced by α-ketoglutarate (α-KG). These genes were further shown to be involved in utilization of α-KG as a sole carbon source under anaerobic conditions. KguS/KguR contributed to the regulation of the target genes with the direct regulation by KguR verified using an electrophoretic mobility shift assay. In addition, oxygen deficiency positively modulated expression of kguS/kguR and its target genes. Taken altogether, this study describes the first UPEC-associated TCS that functions in controlling the utilization of α-ketoglutarate in vivo thereby facilitating UPEC adaptation to life inside the urinary tract. Public Library of Science 2013-06-27 /pmc/articles/PMC3694859/ /pubmed/23825943 http://dx.doi.org/10.1371/journal.ppat.1003428 Text en © 2013 Cai et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Cai, Wentong
Wannemuehler, Yvonne
Dell'Anna, Giuseppe
Nicholson, Bryon
Barbieri, Nicolle L.
Kariyawasam, Subhashinie
Feng, Yaping
Logue, Catherine M.
Nolan, Lisa K.
Li, Ganwu
A Novel Two-Component Signaling System Facilitates Uropathogenic Escherichia coli's Ability to Exploit Abundant Host Metabolites
title A Novel Two-Component Signaling System Facilitates Uropathogenic Escherichia coli's Ability to Exploit Abundant Host Metabolites
title_full A Novel Two-Component Signaling System Facilitates Uropathogenic Escherichia coli's Ability to Exploit Abundant Host Metabolites
title_fullStr A Novel Two-Component Signaling System Facilitates Uropathogenic Escherichia coli's Ability to Exploit Abundant Host Metabolites
title_full_unstemmed A Novel Two-Component Signaling System Facilitates Uropathogenic Escherichia coli's Ability to Exploit Abundant Host Metabolites
title_short A Novel Two-Component Signaling System Facilitates Uropathogenic Escherichia coli's Ability to Exploit Abundant Host Metabolites
title_sort novel two-component signaling system facilitates uropathogenic escherichia coli's ability to exploit abundant host metabolites
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3694859/
https://www.ncbi.nlm.nih.gov/pubmed/23825943
http://dx.doi.org/10.1371/journal.ppat.1003428
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