Getting Across the Cell Envelope: Mycobacterial Protein Secretion

Abstract

Protein secretion is an essential determinant of mycobacterial virulence. Mycobacterium tuberculosis has a unique cell envelope consisting of two lipid bilayers, which requires dedicated protein secretion pathways. The conserved general Sec and Tat translocation systems are responsible for protein transport across the inner membrane and are both essential. Additionally, the accessory Sec pathway specifically contributes to virulence. How transport of Sec/Tat substrates across the outer membrane is accomplished is currently an enigma. In addition to these pathways, M. tuberculosis also developed specialized secretion systems for protein transport across both membranes, the type VII or ESX secretion systems. Here, we discuss our current knowledge about the mechanisms and substrates of these different protein translocation systems and their role in mycobacterial physiology and virulence.

Identification of specific posttranslational O -mycoloylations mediating protein targeting to the mycomembrane

“…Additionally, an outermost layer may exist in some suborder (17,18). The biogenesis and the organization of the Corynebacteriales mycomembrane are far less documented than for the LPScontaining counterpart from Gram-negative outer membranes (19)(20)(21). Notably, very few mycomembrane proteins have been structurally and functionally characterized (10,22), and secretion pathways resulting in mycomembrane association remained an enigma.…”

Mycobacterium Tuberculosis Evolutionary Pathogenesis and its Putative Impact on Drug Development

“…RR: Twin arginine; TAT: Twin-arginine translocation. (A) Data taken from [11,60,64,67]; (B) Data taken from [60,67]. The list of mutants with in vivo growth defects also points to multiple genes implicated in the ESX-1 type VII secretion pathway [30].…”

“…Besides the type VII secretion systems, which represent specialized secretion systems of mycobacteria and related actinobacteria, M. tuberculosis also uses various other secretion pathways for protein export [67] (i.e., the SecA1-mediated general secretory pathway [68], the alternative SecA2-operated pathway [69] and a twin-arginine translocation (TAT) system [70,71]), which might also serve as targets for new drugs [72]. The mycobacterial TAT system, for example, is constituted by a protein complex that includes TatA (Rv2094c) and TatC (Rv2093c), which are essential for the in vitro growth of M. tuberculosis [29,31,71] and are thought to be localized in the plasma membrane (Figure 3).…”

Space: A Final Frontier for Vacuolar Pathogens

“…PknG, an effector of the SecA2 system, is required to block endocytic maturation and create a replicative niche, as phagosomes of pknG and secA2 mutants acidify (63). The ESX-1 secretion system is also required for Mtb virulence, although the functions of its effectors are unknown (62). Taken together, these data indicate that secreted bacterial effector proteins are critical components of the biogenesis of both tight and spacious vacuoles.…”