The Yersinia Virulence Factor YopM Hijacks Host Kinases to Inhibit Type III Effector-Triggered Activation of the Pyrin Inflammasome.

Abstract

Pathogenic Yersinia, including Y. pestis, the agent of plague in humans, and Y. pseudotuberculosis, the related enteric pathogen, deliver virulence effectors into host cells via a prototypical type III secretion system to promote pathogenesis. These effectors, termed Yersinia outer proteins (Yops), modulate multiple host signaling responses. Studies in Y. pestis and Y. pseudotuberculosis have shown that YopM suppresses infection-induced inflammasome activation; however, the underlying molecular mechanism is largely unknown. Here we show that YopM specifically restricts the pyrin inflammasome, which is triggered by the RhoA-inactivating enzymatic activities of YopE and YopT, in Y. pseudotuberculosis-infected macrophages. The attenuation of a yopM mutant is fully reversed in pyrin knockout mice, demonstrating that YopM inhibits pyrin to promote virulence. Mechanistically, YopM recruits and activates the host kinases PRK1 and PRK2 to negatively regulate pyrin by phosphorylation. These results show how a virulence factor can hijack host kinases to inhibit effector-triggered pyrin inflammasome activation.

• Authors: Lawton K Chung, Yong Hwan Park, Yueting Zheng, Igor E Brodsky, Patrick Hearing, Daniel L Kastner, Jae Jin Chae, James B Bliska
• Journal: Cell host & microbe (Cell Host Microbe) Vol. 20 Issue 3 Pg. 296-306 (Sep 14 2016) ISSN: 1934-6069 [Electronic] United States
• PMID: 27569559 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Bacterial Outer Membrane Proteins
• Bacterial Proteins
• Inflammasomes
• Mefv protein, mouse
• Pyrin
• Virulence Factors
• YopT protein, Yersinia
• yopE protein, Yersinia
• yopM protein, Yersinia
• protein kinase N
• Protein Kinase C
• Cysteine Endopeptidases
• rhoA GTP-Binding Protein

Topics

• Animals
• Bacterial Outer Membrane Proteins (metabolism)
• Bacterial Proteins (metabolism)
• Cysteine Endopeptidases (metabolism)
• Host-Pathogen Interactions
• Immune Evasion
• Inflammasomes (antagonists & inhibitors)
• Mice, Inbred C57BL
• Mice, Knockout
• Phosphorylation
• Protein Kinase C (metabolism)
• Protein Processing, Post-Translational
• Pyrin (antagonists & inhibitors, metabolism)
• Survival Analysis
• Virulence
• Virulence Factors (metabolism)
• Yersinia pseudotuberculosis (immunology, pathogenicity)
• Yersinia pseudotuberculosis Infections (microbiology, pathology)
• rhoA GTP-Binding Protein (metabolism)