The Sec Pathways and Exportomes of Mycobacterium tuberculosis

All bacteria utilize pathways to export proteins from the cytoplasm to the bacterial cell envelope or extracellular space. Many exported proteins function in essential physiological processes or in virulence. Consequently, the responsible protein export pathways are commonly essential and/or are important for pathogenesis. The general Sec protein export pathway is conserved and essential in all bacteria, and it is responsible for most protein export. The energy for Sec export is provided by the SecA ATPase. Mycobacteria and some Gram-positive bacteria have two SecA paralogs: SecA1 and SecA2. SecA1 is essential and works with the canonical Sec pathway to perform the bulk of protein export. The nonessential SecA2 exports a smaller subset of proteins and is required for the virulence of pathogens such as Mycobacterium tuberculosis. In this article, we review our current understanding of the mechanism of the SecA1 and SecA2 export pathways and discuss some of their better-studied exported substrates. We focus on proteins with established functions in M. tuberculosis pathogenesis and proteins that suggest potential roles for SecA1 and SecA2 in M. tuberculosis dormancy.