Protein Export into and across the Atypical Diderm Cell Envelope of Mycobacteria

Abstract

General rightsCopyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal ? Take down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.

Transporters Involved in the Biogenesis and Functionalization of the Mycobacterial Cell Envelope

“…164,165 The likelihood of such export machineries spanning the entire cell envelope in mycobacteria is supported in the case of proteins and DNA by the existence of type VII secretion systems. 312 With regard to import, the ATP-driven MCE transport systems, although as yet only partially defined, represent another example of translocation machinery with the potential to span a significant portion of the mycobacterial cell envelope to allow lipid shuttling between the OM and the IM. 282,[284][285][286]288,329,330 Moving forward, a combination of approaches will be required to fill the considerable gaps in knowledge and overcome some of the challenges associated with the unique structure and composition of the mycobacterial cell envelope.…”

Structure and Function of the Mycobacterial Type VII Secretion Systems

“…Substrates of these two pathways contain a characteristic N-terminal signal peptide that is cleaved off upon transport. In addition to this, mycobacteria possess the SecA2 pathway, which exports in concert with the canonical Sec translocon a small subset of proteins (110). While some of the Sec and Tat substrates remain in the putative periplasmic space between the two membranes, other proteins are fully secreted into the extracellular environment by currently unknown secondary mechanisms.…”

“…The initial characterization of T7SSs focused on their critical roles in virulence, such as phagosomal escape and immune modulation. However, in more recent years it has become clear that ESX systems and their substrates play more diverse roles, including horizontal gene transfer, nutrient and metabolite uptake, and cell physiology (50,68,110). While the ESX-2 system has not been characterized, the roles of the other four systems have been studied to various degrees.…”

In Vivo Methods to Study Protein–Protein Interactions as Key Players in Mycobacterium Tuberculosis Virulence

“…ESAT-6 and CFP-10 are both secreted antigens, which play a key role in Mtb virulence [32,33]. The Y2H system helped to demonstrate that EccCa1, EccCb1, and EccD1, which are components of the type VII secretion system ESX-1 [34,35], are required for ESAT-6/CFP-10 secretion [36]. In addition, a single amino acid change in the C-terminal region of CFP-10 was enough to abolish the CFP-10/EccCb1 interaction in the Y2H system, and to prevent secretion of the ESAT-6/CFP-10 complex [37].…”