Vibrio cholerae T3SS Effector VopE Modulates Mitochondrial Dynamics and Innate Immune Signaling by Targeting Miro GTPases

Abstract

SUMMARY The c ellular surveillance-activated detoxification and defenses (cSADD) theory postulates the presence of host surveillance mechanisms that monitor the integrity of common cellular processes and components targeted by pathogen effectors. Being organelles essential for multiple cellular processes, including innate immune responses, mitochondria represent an attractive target for pathogens. We describe a Vibrio cholerae Type 3 secretion system effector VopE that localizes to mitochondria during infection and interferes with the function of mitochondrial Rho GTPases Miro1 and Miro2 by acting as a specific GTPase-activating protein. Miro GTPases modulate mitochondrial dynamics and interference with this functionality effectively blocks innate immune responses that presumably require mitochondria as signaling platforms. Our data indicate that interference with mitochondrial dynamics may be an unappreciated strategy that pathogens use to block host innate immune responses that would otherwise control these bacterial infections. VopE might represent a bacterial effector that targets the cSADD surveillance response.

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