Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 109, Issue 4, Pages 1275-1280Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1109285109
Keywords
rhs element; YD repeat; pathogenesis
Categories
Funding
- National Institute of Health [R01 AI053674, K02 AI065615, R01 AI075191, R21 AI088286, R01 GM071723, R21 AI082406, F30 ES016487]
- National Cancer Institute [CCSG P30 CA060553]
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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-1 beta 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.
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