Computational Analysis of the ESX-1 Region of Mycobacterium tuberculosis: Insights into the Mechanism of Type VII Secretion System

Chandrani Das,Tarini Shankar Ghosh,Sharmila S Mande

doi:10.1371/journal.pone.0027980

Chandrani Das, Tarini Shankar Ghosh + Show 1 more

Open Access

https://doi.org/10.1371/journal.pone.0027980

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Journal: PloS one	Publication Date: Nov 30, 2011
Citations: 86	License type: CC BY 4.0

Affiliation: Tata Consultancy Services (India)

Abstract

Type VII secretion system (T7SS) is a recent discovery in bacterial secretion systems. First identified in Mycobacterium tuberculosis, this secretion system has later been reported in organisms belonging to the Actinomycetales order and even to distant phyla like Firmicutes. The genome of M. tuberculosis H37Rv contains five gene clusters that have evolved through gene duplication events and include components of the T7SS secretion machinery. These clusters are called ESAT-6 secretion system (ESX) 1 through 5. Out of these, ESX-1 has been the most widely studied region because of its pathological importance. In spite of this, the overall mechanism of protein translocation through ESX-1 secretion machinery is not clearly understood. Specifically, the structural components contributing to the translocation through the mycomembrane have not been characterized yet. In this study, we have carried out a comprehensive in silico analysis of the genes known to be involved in ESX-1 secretion pathway and identified putative proteins having high probability to be associated with this particular pathway. Our study includes analysis of phylogenetic profiles, identification of domains, transmembrane helices, 3D folds, signal peptides and prediction of protein-protein associations. Based on our analysis, we could assign probable novel functions to a few of the ESX-1 components. Additionally, we have identified a few proteins with probable role in the initial activation and formation of mycomembrane translocon of ESX-1 secretion machinery. We also propose a probable working model of T7SS involving ESX-1 secretion pathway.

Highlights

Bacterial secretion systems are responsible for the export of virulence factors either to the extracellular environment or directly into the host cell and play a crucial role in the virulence of a pathogen [1]
Orthologs of each protein belonging to M. tuberculosis H37Rv were first identified across other mycobacterial species
While Rv3866 has been proposed to be involved in the transcriptional activation of the secretion machinery, Rv3876 has been predicted to be a negative regulator of this machinery

Summary

Introduction

Bacterial secretion systems are responsible for the export of virulence factors either to the extracellular environment or directly into the host cell and play a crucial role in the virulence of a pathogen [1]. Seven categories of secretion systems (Type I to Type VII) have been identified in bacteria [1,2,3]. These secretion systems differ in terms of the secreted effector molecules, and in their structural components. The most recently categorized Type VII secretion system (T7SS) is observed to be present in the Grampositive species, mostly belonging to the Actinomycetales order [4]. The T7SS has been shown to secrete proteins lacking classical signal peptides in contrast to that observed in Type II, IV and V secretion systems. Most of the proteins secreted by T7SS follow a pairwise dependency, both for secretion and function [8]

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