Take five — Type VII secretion systems of Mycobacteria

Abstract

Mycobacteria use type VII secretion (T7S) systems to secrete proteins across their complex cell envelope. Pathogenic mycobacteria, such as the notorious pathogen Mycobacterium tuberculosis, have up to five of these secretion systems, named ESX-1 to ESX-5. At least three of these secretion systems are essential for mycobacterial virulence and/or viability. Elucidating T7S is therefore essential to understand the success of M. tuberculosis and other pathogenic mycobacteria as pathogens, and could be instrumental to identify novel targets for drug- and vaccine-development. Recently, significant progress has been achieved in the identification of T7S substrates and a general secretion motif. In addition, a start has been made with unraveling the mechanism of secretion and the structural analysis of the different subunits. This review summarizes these recent findings, which are incorporated in a working model of this complex machinery. This article is part of a Special Issue entitled: Protein trafficking and secretion in bacteria. Guest Editors: Anastassios Economou and Ross Dalbey.

Comparative genome analysis of Streptococcus iniae DX09 reveals new insights into niche adaptation and competitive host colonisation ability

“…ESX-1 is partially missing in the vaccine strain Mycobacterium bovis Bacille Calmette-Guérin [32], indicating a contribution to virulence. Previous investigations have demonstrated a crucial role of T7SS in bacterial survival within the host [21,23,31,32], consistent with transmission electron micrographs of interactions between S. iniae DX09 and spleen cells from diseased catfish. Moreover, considerable evidence is available supporting essential roles of the actinobacterial ESS protein secretion system in virulence [26][27][28][29].…”

“…Pathogenic mycobacteria generally possess up to five different T7SS (ESX-1, ESX-2, ESX-3, ESX-4 and ESX-5), which have possibly evolved via gene duplication [31]. Several studies suggest that ESX-1, the first T7SS identified, strongly influences host-pathogen interactions, in particular, the ability of bacteria to escape the phago-vacuole of infected cells (macrophages and dendritic cells) [23]. ESX-1 is partially missing in the vaccine strain Mycobacterium bovis Bacille Calmette-Guérin [32], indicating a contribution to virulence.…”

“…T7SS, specifically present in Gram-positive bacteria [21], is proposed to be involved in translocation of proteins (generally virulence factors) to the extracellular environment [22]. T7SS was initially described and termed the 'ESX protein secretion system' in pathogenic mycobacteria [23] belonging to the class Actinobacteria with high GC content. Subsequently, a related secretion system (ESS protein secretion) was detected in some Firmicutes bacteria, including Staphylococcus aureus [24][25][26][27][28][29], Listeria monocytogenes [21,30], Bacillus subtilis [21,30] and Streptococcus agalactiae [21,30].…”

An outer membrane channel protein of Mycobacterium tuberculosis with exotoxin activity

“…However, the only known secretion systems capable of translocating proteins across both M. tuberculosis membranes are the type VII secretion systems encoded by esx operons. Although inner membrane proteins of ESX secretion systems have been characterized (16), channel proteins that are required for protein translocation across the outer membrane are currently unknown in M. tuberculosis. We hypothesized that deletion or inactivation of outer membrane channel proteins in M. tuberculosis may result in increased antibiotic resistance, as has been described for Gram-negative bacteria and Mycobacterium smegmatis (17,18).…”

Structure of a PE–PPE–EspG complex fromMycobacterium tuberculosisreveals molecular specificity of ESX protein secretion

“…Along with additional species/lineage-specific factors, such as the mycobacterial PE and PPE proteins, these components have been proposed to assemble in the plasma membrane, where they translocate specific protein substrates to the cell surface (or to the periplasmic space of mycobacteria) (figure 4B of ref. 18). The Mtb genome encodes five distinct but evolutionarily related type VII/ESX systems (ESX-1 to ESX-5) at different loci around the genome, and the primary attenuating mutation in the Mycobacterium bovis bacillus Calmette-Guérin vaccine strain is a deletion of a large segment of the ESX-1 locus (19).…”