Esx Systems and the Mycobacterial Cell Envelope: What's the Connection?

Mycobacterial 6-kDa early secreted antigenic target (ESAT-6) system (ESX) exporters transport proteins across the cytoplasmic membrane. Many proteins transported by ESX systems are then translocated across the mycobacterial cell envelope and secreted from the cell. Although the mechanism underlying protein transport across the mycolate outer membrane remains elusive, the ESX systems are closely connected with and localize to the cell envelope. Links between ESX-associated proteins, cell wall synthesis, and the maintenance of cell envelope integrity have been reported. Genes encoding the ESX systems and those required for biosynthesis of the mycobacterial envelope are coregulated. Here, we review the interplay between ESX systems and the mycobacterial cell envelope.