An rhs gene of Pseudomonas aeruginosa encodes a virulence protein that activates the inflammasome.
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.
Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Vanderlene L
VL
Kung
Sonal
S
Khare
Christian
C
Stehlik
Elizabeth M
EM
Bacon
Ami J
AJ
Hughes
Alan R
AR
Hauser
D000818:Animals; D001427:Bacterial Toxins / Q000235:genetics*; D002460:Cell Line; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D015151:Immunoblotting; D058847:Inflammasomes / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D053583:Interleukin-1beta / Q000378:metabolism; D013058:Mass Spectrometry; D051379:Mice; D008807:Mice, Inbred BALB C; D010586:Phagocytes / Q000378:metabolism; D011014:Pneumonia / Q000276:immunology* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D053719:Tandem Mass Spectrometry; D014162:Transfection; D037521:Virulence Factors / Q000235:genetics*
D001427:Bacterial Toxins; D058847:Inflammasomes; D036341:Intercellular Signaling Peptides and Proteins; D053583:Interleukin-1beta; D037521:Virulence Factors; C118370:interleukin-18 binding protein