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SIMM discovers a key pathogenic signal transduction pathway of Pseudomonas aeruginosa
Update time: 2014-09-09
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Pseudomonas aeruginosa is the main pathogen that cause hospital infection, immunodeficiency and cystic fibrosis(CF), it can cause an acute and chronic infection.The researchers from LAN Lefu's group of SIMM,Hainan University,Nanjing University , State Key Laboratory of Respiratory Diseases and the First Affiliated Hospital of Guangzhou Medical College, the University of Chicago and the University of North Dakota uncovered a signal transduction pathway ,BfmS/BfmR/RhlR,for the regulation of rhl Quorum Sensing and Bacterial Virulence in Pseudomonas aeruginosa.This research have been published in the international journal of etiology (PLOS Pathogens) on August 28, 2014.

In this study, we demonstrate that BfmS and BfmR constitute a two-component system signal transduction,wild type BfmS has the phosphatase activity,and it controls the transcriptional regulation activity of BfmR through negative adjustment the phosphorylation of 55th aspartate residue of the BfmR protein.The inactivation of bfmSgene cause the excessive phosphorylation of BfmR, and the phosphorylation BfmR directly binds to the promoter of rhlRgene(encoding the rhlQS transcriptional regulator RhlR) and decreases the expression of the rhlR, causing the inhibition of the rhlQS system,ontributing the expression of the virulence factors such as rhamnolipid and pyocyanindecrease sharply, and the acute infection ability decrease significantly. In addition, the excessive phosphorylation of BfmR dramatically increases biofilm formation ( the important decision factor of chronic infections in bacteria)in P.aeruginosa.In long-term infection of the cystic fibrosis (CF)lungs, bfmS gene had been missense mutation which cause its function reverse (reverse – of – function): the mutational bfmS protein are mainly with kinase activity rather than the phosphatase activity, leading to the height of the phosphorylation of BfmR and have been activated.It suggests that BfmS may play an important role in mediating the switch between the acute and chronic infection life styles of P.aeruginosa.

The first authors of this paper Cao Qiao(the student of Hainan University),Wang Yue(the student of Nanjing University) contributed aqually to this work.This work was financially supported by National Natural Science Foundation of China Grants, Shanghai Committee of Science andTechnology grants.

Original article:

http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1004340

Model of the regulatory networks involving BfmRS inP. aeruginosa

 

 
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