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A Novel Signal Transduction Pathway that Modulates rhl Quorum Sensing and Bacterial Virulence in Pseudomonas aeruginosa

文献类型：期刊论文

作者Cao, Qiao2,3; Wang, Yue1,3; Chen, Feifei3; Xia, Yongjie3; Lou, Jingyu3; Zhang, Xue3; Yang, Nana3; Sun, Xiaoxu3; Zhang, Qin4,5; Zhuo, Chao4,5
刊名PLOS PATHOGENS
出版日期2014-08
卷号10期号:8
ISSN号1553-7366
DOI10.1371/journal.ppat.1004340
文献子类Article
英文摘要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.
WOS关键词CYSTIC-FIBROSIS PATIENTS ; GENE-EXPRESSION ; ANTIBIOTIC-RESISTANCE ; REGULATOR RHPR ; SYSTEM ; INFECTION ; ADAPTATION ; STRESS ; IDENTIFICATION ; ENVIRONMENT
资助项目National Natural Science Foundation of China[31270126] ; Shanghai Committee of Science and Technology[12JC1410200] ; National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program"[2014ZX09507009-015] ; National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program"[2013ZX09507-004] ; Hundred Talents Program of the Chinese Academy of Sciences[00000000] ; Flight Attendant Medical Research Institute (FAMRI)[103007] ; NIH[AI101973-01] ; NIH[AI097532-01A1]
WOS研究方向Microbiology ; Parasitology ; Virology
语种英语
WOS记录号WOS:000341576300051
出版者PUBLIC LIBRARY SCIENCE
源URL[http://119.78.100.183/handle/2S10ELR8/276954]  
专题药理学第三研究室
通讯作者Cao, Qiao
作者单位1.Nanjing Univ, Sch Life Sci, State Key Lab Pharmaceut Biotechnol, Inst Chem & BioMed Sci, Nanjing 210008, Jiangsu, Peoples R China;
2.Hainan Univ, Haikou, Hainan, Peoples R China;
3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China;
4.Guangzhou Med Univ, State Key Lab Resp Dis, Guangzhou, Guangdong, Peoples R China;
5.Guangzhou Med Univ, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China;
6.Univ Chicago, Dept Chem, Chicago, IL 60637 USA;
7.Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USA;
8.Univ N Dakota, Sch Med & Hlth Sci, Dept Basic Sci, Grand Forks, ND 58201 USA
推荐引用方式
GB/T 7714		 Cao, Qiao,Wang, Yue,Chen, Feifei,et al. A Novel Signal Transduction Pathway that Modulates rhl Quorum Sensing and Bacterial Virulence in Pseudomonas aeruginosa[J]. PLOS PATHOGENS,2014,10(8).
APA Cao, Qiao.,Wang, Yue.,Chen, Feifei.,Xia, Yongjie.,Lou, Jingyu.,...&Lan, Lefu.(2014).A Novel Signal Transduction Pathway that Modulates rhl Quorum Sensing and Bacterial Virulence in Pseudomonas aeruginosa.PLOS PATHOGENS,10(8).
MLA Cao, Qiao,et al."A Novel Signal Transduction Pathway that Modulates rhl Quorum Sensing and Bacterial Virulence in Pseudomonas aeruginosa".PLOS PATHOGENS 10.8(2014).

入库方式： OAI收割

来源：上海药物研究所

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