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

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

Author information

1
Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.

Abstract

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.

PMID:
22232685
PMCID:
PMC3268321
DOI:
10.1073/pnas.1109285109
[Indexed for MEDLINE]
Free PMC Article

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