VopE, a Vibrio cholerae Type III Effector, Attenuates the Activation of CWI-MAPK Pathway in Yeast Model System.

Leela K Bankapalli,Saumya Raychaudhuri,Rahul C Mishra

doi:10.3389/fcimb.2017.00082

Leela K Bankapalli, Saumya Raychaudhuri + Show 1 more

Open Access

https://doi.org/10.3389/fcimb.2017.00082

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Abstract

VopE, a mitochondrial targeting T3SS effector protein of Vibrio cholerae, perturbs innate immunity by modulating mitochondrial dynamics. In the current study, ectopic expression of VopE was found to be toxic in a yeast model system and toxicity was further aggravated in the presence of various stressors. Interestingly, a VopE variant lacking predicted mitochondrial targeting sequence (MTS) also exhibited partial lethality in the yeast system. With the aid of yeast genetic tools and different stressors, we have demonstrated that VopE and its derivative VopEΔMTS modulate cell wall integrity (CWI-MAPK) signaling pathway and have identified several critical residues contributing to the lethality of VopE. Furthermore, co-expression of two effectors VopEΔMTS and VopX, interfering with the CWI-MAPK cellular pathway can partially suppress the VopX mediated yeast growth inhibition. Taken together, these results suggest that VopE alters signaling through the CWI-MAPK pathway, and demonstrates the usefulness of yeast model system to gain additional insights on the functionality of VopE.

Highlights

The effectiveness of a microbe as a pathogen is largely dependent on its ability to subvert the host defense mechanism
It has been demonstrated that VopE by virtue of a typical mitochondrial targeting sequence (MTS) at the N-terminus localizes to the mitochondria where it alters mitochondrial dynamics
In this study the budding yeast has been exploited as a model organism for functional exploration of VopE, a type 3 secretion system (T3SS) effector protein of V. cholerae

Summary

Introduction

The effectiveness of a microbe as a pathogen is largely dependent on its ability to subvert the host defense mechanism. Multiple lines of converging evidences clearly demonstrate the evolution of unique functional domains and motifs in several T3SS effector proteins, that empower diverse pathogens to usurp disparate host cellular processes (Dean, 2011; Salomon et al, 2013). A T3SS secretion system and 11 bona fide effector proteins with unique structural and functional features have been reported in Vibrio cholerae strains belonging to diverse serogroups and role of these effector proteins in pathogenesis have been studied in vitro and in vivo using animal and yeast model system (Dziejman et al, 2005; Tam et al, 2007; Tripathi et al, 2010; Alam et al, 2011) One such effector protein VopE, a close homolog of the Yersinia T3SS effector protein YopE, disrupts the integrity of tight junctions by modulating actin homeostasis, promoting pathogenecity of V. cholerae strain AM-19226 (Tam et al, 2010; Shin et al, 2011). It has been demonstrated that VopE by virtue of a typical mitochondrial targeting sequence (MTS) at the N-terminus localizes to the mitochondria where it alters mitochondrial dynamics

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