Protein export into and across the atypical diderm cell envelope of mycobacteria

Mycobacteria are Actinobacteria, which is a phylum of high-GC Gram-positive bacteria. Among the wide range of Mycobacterium spp. are several important pathogens. Most notable of these is Mycobacterium tuberculosis, the causative agent of tuberculosis (TB). Although the number of TB cases and deaths show a declining trend in the past decade, the World Health Organization recently warned that “current actions and investments in research are falling far short” (http://www.who.int/mediacentre/news/releases/2016/tuberculosis-investments-short/en/). Over 1.3 million deaths and up to 10.0 million new infections were attributed to M. tuberculosis in 2017, which makes M. tuberculosis the most deadly infectious agent in the world, surpassing HIV and the malaria parasite (1). One issue facing efforts to control TB is that the live attenuated bacillus Calmette-Guérin (BCG) vaccine strain is not able to provide lifelong protection against M. tuberculosis (2). Another problem is the increased incidence of infections caused by multidrug-resistant M. tuberculosis strains. Consequently, major research efforts focus on understanding M. tuberculosis pathogenesis and physiology to advance the development of new anti-TB vaccines and antibiotics.