title: The Yersinia virulence effector YopM binds caspase-1 to arrest inflammasome assembly and processing.
abstract: Inflammasome assembly activates caspase-1 and initiates the inflammatory cell death program pyroptosis, which is protective against numerous pathogens. Consequently, several pathogens, including the plague causing bacterium Yersinia pestis, avoid activating this pathway to enhance their virulence. However, bacterial molecules that directly modulate the inflammasome have yet to be identified. Examining the contribution of Yersinia type III secretion effectors to caspase-1 activation, we identified the leucine-rich repeat effector YopM as a potent antagonist of both caspase-1 activity and activation. YopM directly binds caspase-1, which both inhibits caspase-1 activity and sequesters it to block formation of the mature inflammasome. Caspase-1 activation antagonizes Yersinia survival in vivo, and consequently YopM inhibition of caspase-1 is required for Yersinia pathogenesis. Thus, a bacterium obstructs pyroptosis utilizing a direct mechanism of caspase-1 inhibition that is distinct from known viral or host inhibitors.
authors.affiliation: Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Christopher N
authors.initials: CN
authors.lastname: LaRock
authors.forename: Brad T
authors.initials: BT
authors.lastname: Cookson
mesh_terms: D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism*; D057131:Immune Evasion; D058847:Inflammasomes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D050296:Microbial Viability; D037521:Virulence Factors / Q000378:metabolism*; D015010:Yersinia pestis / Q000276:immunology* / Q000472:pathogenicity*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D058847:Inflammasomes; D037521:Virulence Factors; C060772:yopM protein, Yersinia; D020170:Caspase 1