An rhs gene of Pseudomonas aeruginosa encodes a virulence protein that activates the inflammasome

Proc Natl Acad Sci U S A. 2012 Jan 24;109(4):1275-80. doi: 10.1073/pnas.1109285109. Epub 2012 Jan 9.


The rhs genes are a family of enigmatic composite genes, widespread among Gram-negative bacteria. In this study, we characterized rhsT, a Pseudomonas aeruginosa rhs gene that encodes a toxic protein. Expression of rhsT was induced upon contact with phagocytic cells. The RhsT protein was exposed on the bacterial surface and translocated into phagocytic cells; these cells subsequently underwent inflammasome-mediated death. Moreover, RhsT enhanced host secretion of the potent proinflammatory cytokines IL-1β and IL-18 in an inflammasome-dependent manner. In a mouse model of acute pneumonia, infection with a P. aeruginosa strain lacking rhsT was associated with less IL-18 production, fewer recruited leukocytes, reduced pulmonary bacterial load, and enhanced animal survival. Thus, rhsT encodes a virulence determinant that activates the inflammasome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Toxins / genetics*
  • Cell Line
  • Flow Cytometry
  • Fluorescent Antibody Technique, Indirect
  • Immunoblotting
  • Inflammasomes / metabolism*
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-1beta / metabolism
  • Mass Spectrometry
  • Mice
  • Mice, Inbred BALB C
  • Phagocytes / metabolism
  • Pneumonia / immunology*
  • Pneumonia / microbiology
  • Pseudomonas aeruginosa / genetics*
  • Real-Time Polymerase Chain Reaction
  • Tandem Mass Spectrometry
  • Transfection
  • Virulence Factors / genetics*


  • Bacterial Toxins
  • Inflammasomes
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-1beta
  • Virulence Factors
  • interleukin-18 binding protein