Modular Organization of the ESX-5 Secretion System in Mycobacterium tuberculosis.

Swati Shah,Volker Briken

doi:10.3389/fcimb.2016.00049

Abstract

Mycobacteria utilize type VII secretion systems (T7SS) to export many of their important virulence proteins. The T7SS encompasses five homologous secretion systems (ESX-1 to ESX-5). Most pathogenic mycobacterial species, including the human pathogen Mycobacterium tuberculosis, possess all five ESX systems. The ESX-1, -3, and -5 systems are important for virulence of mycobacteria but the molecular mechanisms of their secretion apparatus and the identity and activity of secreted effector proteins are not well characterized. The different ESX systems show similarities in gene composition due to their common phylogenetic origin but recent studies demonstrate mechanistic as well as functional variations between the systems. For example, the ESX-1 system is involved in lysis of the phagosomal membrane and phagosomal escape of the bacteria while the ESX-5 system is required for mycobacterial cell wall stability and host cell lysis. Mechanistically, the ESX-1 substrates show interdependence during secretion while the ESX-5 system may use a duplicated four-gene region (ESX-5a) as an accessory system for transport of a subset of proteins of the ESX-5 secretome. In the present review we will provide an overview of the molecular components of the T7SS and their function with a particular focus on the ESX-5 system.

Highlights

Only the ESX-1, ESX-3, and ESX-5 systems have been proven to be involved in protein secretion (Pym et al, 2002; Stanley, 2003; Abdallah et al, 2006, 2009; Siegrist et al, 2009; Daleke et al, 2012; Tufariello et al, 2016) while no evidence of active secretion in ESX-2 or ESX-4 systems has been found to date
The ESX-5 secretion system is involved in the export of the vast majority of PE/PPE proteins to the cell surface and culture supernatant
We provide evidence that at least one of the four-gene, esx gene cluster duplicated from the ESX-5 system acts as an accessory region that is required for the secretion of a subset of the ESX-5 secretome

Summary

Swati Shah and Volker Briken *

The Ohio State University, USA Robert B. Mycobacteria utilize type VII secretion systems (T7SS) to export many of their important virulence proteins. The T7SS encompasses five homologous secretion systems (ESX-1 to ESX-5). The ESX-1, -3, and -5 systems are important for virulence of mycobacteria but the molecular mechanisms of their secretion apparatus and the identity and activity of secreted effector proteins are not well characterized. The ESX-1 substrates show interdependence during secretion while the ESX-5 system may use a duplicated four-gene region (ESX-5a) as an accessory system for transport of a subset of proteins of the ESX-5 secretome. In the present review we will provide an overview of the molecular components of the T7SS and their function with a particular focus on the ESX-5 system

THE TYPE VII SECRETION SYSTEM COMPONENTS

Findings

CONCLUSIONS