Journal Article

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

Khare, Sonal, Stehlik, Christian, Hauser, Alan R., Kung, Vanderlene L., Bacon, Elizabeth M., Hughes, Ami J.

2012

Overview

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-18and 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.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: Animal models / Animals / Bacteria / Bacterial Toxins - genetics / Biological Sciences / Cell Line / Cell lines / Cell survival / Cells / Cytokines / Flow Cytometry / Fluorescent Antibody Technique, Indirect / Gene expression / Gram-negative bacteria / Immunoblotting / Infection / Infections / Inflammasomes - metabolism / Inflammation / Intercellular Signaling Peptides and Proteins / Interleukin 1 / Interleukin 18 / Interleukin-1beta - metabolism / Leukocytes / Lung / Lungs / Mass Spectrometry / Mice / Mice, Inbred BALB C / Phagocytes / Phagocytes - metabolism / Pneumonia / Pneumonia - immunology / Pneumonia - microbiology / Proteins / Pseudomonas aeruginosa / Pseudomonas aeruginosa - genetics / Real-Time Polymerase Chain Reaction / Rodents / Secretion / Tandem Mass Spectrometry / Toxins / Transfection / Virulence / Virulence Factors - genetics