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

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

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Author(s)

  • Qiao Cao
  • Yue Wang
  • Feifei Chen
  • Yongjie Xia
  • Jingyu Lou
  • Xue Zhang
  • Nana Yang
  • Xiaoxu Sun
  • Qin Zhang
  • Chao Zhuo
  • Xi Huang
  • Cai-Guang Yang
  • Yan Ye
  • Jing Zhao
  • Min Wu
  • Lefu Lan

Detail(s)

Original languageEnglish
Article numbere1004340
Journal / PublicationPLoS Pathogens
Volume10
Issue number8
Publication statusPublished - Aug 2014
Externally publishedYes

Link(s)

Abstract

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.

Research Area(s)

Citation Format(s)

A Novel Signal Transduction Pathway that Modulates rhl Quorum Sensing and Bacterial Virulence in Pseudomonas aeruginosa. / Cao, Qiao; Wang, Yue; Chen, Feifei et al.
In: PLoS Pathogens, Vol. 10, No. 8, e1004340, 08.2014.

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

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