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A Novel Signal Transduction Pathway that Modulates rhl Quorum Sensing and Bacterial Virulence in Pseudomonas aeruginosa
The rhl quorum-sensing (QS) system plays critical roles in the pathogenesis of P. aeruginosa. However, the regulatory effects that occur directly upstream of the rhl QS system are poorly understood. Here, we show that deletion of gene encoding for the two-component sensor BfmS leads to the activatio...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4148453/ https://www.ncbi.nlm.nih.gov/pubmed/25166864 http://dx.doi.org/10.1371/journal.ppat.1004340 |
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author | Cao, Qiao Wang, Yue Chen, Feifei Xia, Yongjie Lou, Jingyu Zhang, Xue Yang, Nana Sun, Xiaoxu Zhang, Qin Zhuo, Chao Huang, Xi Deng, Xin Yang, Cai-Guang Ye, Yan Zhao, Jing Wu, Min Lan, Lefu |
author_facet | Cao, Qiao Wang, Yue Chen, Feifei Xia, Yongjie Lou, Jingyu Zhang, Xue Yang, Nana Sun, Xiaoxu Zhang, Qin Zhuo, Chao Huang, Xi Deng, Xin Yang, Cai-Guang Ye, Yan Zhao, Jing Wu, Min Lan, Lefu |
author_sort | Cao, Qiao |
collection | PubMed |
description | The rhl quorum-sensing (QS) system plays critical roles in the pathogenesis of P. aeruginosa. However, the regulatory effects that occur directly upstream of the rhl QS system are poorly understood. Here, we show that deletion of gene encoding for the two-component sensor BfmS leads to the activation of its cognate response regulator BfmR, which in turn directly binds to the promoter and decreases the expression of the rhlR gene that encodes the QS regulator RhlR, causing the inhibition of the rhl QS system. In the absence of bfmS, the Acka-Pta pathway can modulate the regulatory activity of BfmR. In addition, BfmS tunes the expression of 202 genes that comprise 3.6% of the P. aeruginosa genome. We further demonstrate that deletion of bfmS causes substantially reduced virulence in lettuce leaf, reduced cytotoxicity, enhanced invasion, and reduced bacterial survival during acute mouse lung infection. Intriguingly, specific missense mutations, which occur naturally in the bfmS gene in P. aeruginosa cystic fibrosis (CF) isolates such as DK2 strains and RP73 strain, can produce BfmS variants (BfmS(L181P), BfmS(L181P/E376Q), and BfmS(R393H)) that no longer repress, but instead activate BfmR. As a result, BfmS variants, but not the wild-type BfmS, inhibit the rhl QS system. This study thus uncovers a previously unexplored signal transduction pathway, BfmS/BfmR/RhlR, for the regulation of rhl QS in P. aeruginosa. We propose that BfmRS TCS may have an important role in the regulation and evolution of P. aeruginosa virulence during chronic infection in CF lungs. |
format | Online Article Text |
id | pubmed-4148453 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-41484532014-08-29 A Novel Signal Transduction Pathway that Modulates rhl Quorum Sensing and Bacterial Virulence in Pseudomonas aeruginosa Cao, Qiao Wang, Yue Chen, Feifei Xia, Yongjie Lou, Jingyu Zhang, Xue Yang, Nana Sun, Xiaoxu Zhang, Qin Zhuo, Chao Huang, Xi Deng, Xin Yang, Cai-Guang Ye, Yan Zhao, Jing Wu, Min Lan, Lefu PLoS Pathog Research Article The rhl quorum-sensing (QS) system plays critical roles in the pathogenesis of P. aeruginosa. However, the regulatory effects that occur directly upstream of the rhl QS system are poorly understood. Here, we show that deletion of gene encoding for the two-component sensor BfmS leads to the activation of its cognate response regulator BfmR, which in turn directly binds to the promoter and decreases the expression of the rhlR gene that encodes the QS regulator RhlR, causing the inhibition of the rhl QS system. In the absence of bfmS, the Acka-Pta pathway can modulate the regulatory activity of BfmR. In addition, BfmS tunes the expression of 202 genes that comprise 3.6% of the P. aeruginosa genome. We further demonstrate that deletion of bfmS causes substantially reduced virulence in lettuce leaf, reduced cytotoxicity, enhanced invasion, and reduced bacterial survival during acute mouse lung infection. Intriguingly, specific missense mutations, which occur naturally in the bfmS gene in P. aeruginosa cystic fibrosis (CF) isolates such as DK2 strains and RP73 strain, can produce BfmS variants (BfmS(L181P), BfmS(L181P/E376Q), and BfmS(R393H)) that no longer repress, but instead activate BfmR. As a result, BfmS variants, but not the wild-type BfmS, inhibit the rhl QS system. This study thus uncovers a previously unexplored signal transduction pathway, BfmS/BfmR/RhlR, for the regulation of rhl QS in P. aeruginosa. We propose that BfmRS TCS may have an important role in the regulation and evolution of P. aeruginosa virulence during chronic infection in CF lungs. Public Library of Science 2014-08-28 /pmc/articles/PMC4148453/ /pubmed/25166864 http://dx.doi.org/10.1371/journal.ppat.1004340 Text en © 2014 Cao 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 Cao, Qiao Wang, Yue Chen, Feifei Xia, Yongjie Lou, Jingyu Zhang, Xue Yang, Nana Sun, Xiaoxu Zhang, Qin Zhuo, Chao Huang, Xi Deng, Xin Yang, Cai-Guang Ye, Yan Zhao, Jing Wu, Min Lan, Lefu A Novel Signal Transduction Pathway that Modulates rhl Quorum Sensing and Bacterial Virulence in Pseudomonas aeruginosa |
title | A Novel Signal Transduction Pathway that Modulates rhl Quorum Sensing and Bacterial Virulence in Pseudomonas aeruginosa
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title_full | A Novel Signal Transduction Pathway that Modulates rhl Quorum Sensing and Bacterial Virulence in Pseudomonas aeruginosa
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title_fullStr | A Novel Signal Transduction Pathway that Modulates rhl Quorum Sensing and Bacterial Virulence in Pseudomonas aeruginosa
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title_full_unstemmed | A Novel Signal Transduction Pathway that Modulates rhl Quorum Sensing and Bacterial Virulence in Pseudomonas aeruginosa
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title_short | A Novel Signal Transduction Pathway that Modulates rhl Quorum Sensing and Bacterial Virulence in Pseudomonas aeruginosa
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title_sort | novel signal transduction pathway that modulates rhl quorum sensing and bacterial virulence in pseudomonas aeruginosa |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4148453/ https://www.ncbi.nlm.nih.gov/pubmed/25166864 http://dx.doi.org/10.1371/journal.ppat.1004340 |
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