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

PLoS Pathogens

Min Wu¹  Yan Ye²  Cai-Guang Yang³  Qiao Cao³  Yongjie Xia⁴  Lefu Lan⁴  Chao Zhuo⁵  Jing Zhao⁵  Jingyu Lou⁵  Xue Zhang⁵  Qin Zhang⁵  Xiaoxu Sun⁵  Nana Yang⁵  Yue Wang⁵  Feifei Chen⁵  Xi Huang⁶  Xin Deng⁶ 

[1] Department of Basic Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota, United States of America;Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois, United States of America;Hainan University, Haikou, Hainan, China;Institute of Chemistry and BioMedical Sciences, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China;Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China;State Key Laboratory of Respiratory Diseases and the First Affiliated Hospital of Guangzhou Medical College, Guangzhou, China

关键词: Pseudomonas aeruginosa;    Gene expression;    Regulator genes;    Glucose;    Polymerase chain reaction;    Promoter regions;    Cystic fibrosis;    Gene regulation;   

DOI  :  10.1371/journal.ppat.1004340

学科分类：生物科学（综合）

来源: Public Library of Science

【 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 (BfmSL181P, BfmSL181P/E376Q, and BfmSR393H) 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.

【 授权许可】

CC BY