Protein Export Systems of Mycobacterium Tuberculosis : Novel Targets for Drug Development?

Abstract

Protein export is essential in all bacteria and many bacterial pathogens depend on specialized protein export systems for virulence. In Mycobacterium tuberculosis, the etiological agent of the disease tuberculosis, the conserved general secretion (Sec) and twin-arginine translocation (Tat) pathways perform the bulk of protein export and are both essential. M. tuberculosis also has specialized export pathways that transport specific subsets of proteins. One such pathway is the accessory SecA2 system, which is important for M. tuberculosis virulence. There are also specialized ESX export systems that function in virulence (ESX-1) or essential physiologic processes (ESX-3). The increasing prevalence of drug-resistant M. tuberculosis strains makes the development of novel drugs for tuberculosis an urgent priority. In this article, we discuss our current understanding of the protein export systems of M. tuberculosis and consider the potential of these pathways to be novel targets for tuberculosis drugs.

ADP-dependent Conformational Changes Distinguish Mycobacterium tuberculosis SecA2 from SecA1

“…Protein export pathways are promising therapeutic targets that have yet to be fully exploited in this bacterium (1). The M. tuberculosis SecA2 protein is one such target.…”

Genetically Programmable Pathogen Sense and Destroy

“…Type VI [73,74] and Type VII (only identified in Mycobacterium spp. ; [75]) secretion systems have only been recently identified and the details about the secretion mechanism are still emerging. Type II and V are two-step secretion mechanisms.…”

Computational Approach for Locating Effective Cyanobacterial Compounds against Mycobacterium Tuberculosis

“…9,10 In the cytoplasmic step, the synthesis of UDP-MurNAc from UDP-GlcNAc is mediated by MurA ligase (UDP-N-acetylglucosamine 1-carboxyvinyl transferase), which was used as a suitable target for the drug development attempt. [9][10][11][12] Previously for drug development, to address drug resistant strains of the Gram-positive bacterium, Enterococcus faecalis as well as, of M. leprae, Mur ligases were shown as target enzymes in molecular docking attempts. 13,14 Obviously, an in silico computation would help locating a suitable control agent without the hit-andmiss method, which is often followed in drug targeting attempts; in vivo attempts would follow by apothecary, after being suitably indicated by computational work.…”