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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2013-01-01
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Series: | PLoS Pathogens |
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doaj-659dac7c2aa2487ba4fc36013c9330ea2020-11-25T00:11:44ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742013-01-0196e100342810.1371/journal.ppat.1003428A novel two-component signaling system facilitates uropathogenic Escherichia coli's ability to exploit abundant host metabolites.Wentong CaiYvonne WannemuehlerGiuseppe Dell'annaBryon NicholsonNicolle L BarbieriSubhashinie KariyawasamYaping FengCatherine M LogueLisa K NolanGanwu LiTwo-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.http://europepmc.org/articles/PMC3694859?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Wentong Cai Yvonne Wannemuehler Giuseppe Dell'anna Bryon Nicholson Nicolle L Barbieri Subhashinie Kariyawasam Yaping Feng Catherine M Logue Lisa K Nolan Ganwu Li |
spellingShingle |
Wentong Cai Yvonne Wannemuehler Giuseppe Dell'anna Bryon Nicholson Nicolle L Barbieri Subhashinie Kariyawasam Yaping Feng Catherine M Logue Lisa K Nolan Ganwu Li A novel two-component signaling system facilitates uropathogenic Escherichia coli's ability to exploit abundant host metabolites. PLoS Pathogens |
author_facet |
Wentong Cai Yvonne Wannemuehler Giuseppe Dell'anna Bryon Nicholson Nicolle L Barbieri Subhashinie Kariyawasam Yaping Feng Catherine M Logue Lisa K Nolan Ganwu Li |
author_sort |
Wentong Cai |
title |
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_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_sort |
novel two-component signaling system facilitates uropathogenic escherichia coli's ability to exploit abundant host metabolites. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Pathogens |
issn |
1553-7366 1553-7374 |
publishDate |
2013-01-01 |
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. |
url |
http://europepmc.org/articles/PMC3694859?pdf=render |
work_keys_str_mv |
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