Mycobacterium tuberculosis PE_PGRS20 and PE_PGRS47 Proteins Inhibit Autophagy by Interaction with Rab1A

Tuberculosis is a significant global infectious disease caused by infection of the lungs with Mycobacterium tuberculosis, which then resides and replicates mainly within host phagocytic cells. Autophagy is a complex host cellular process that helps control intracellular infections and enhance innate and adaptive immune responses. During coevolution with humans, M. tuberculosis has acquired various mechanisms to inhibit host cellular processes, including autophagy. We identified two related M. tuberculosis proteins, PE_PGRS20 and PE_PGRS47, as the first reported examples of specific mycobacterial effectors interfering with the initiation stage of autophagy. Autophagy regulation by these PE_PGRS proteins leads to increased bacterial survival in phagocytic cells and increased autophagic degradation of mycobacterial antigens to stimulate adaptive immune responses. A better understanding of how M. tuberculosis regulates autophagy in host cells could facilitate the design of new and more effective therapeutics or vaccines against tuberculosis.