Mycobacterium tuberculosis Rv0927c inhibits proliferation and promotes intrinsic apoptosis of alveolar epithelial cell through targeting mitochondrial TUFM

Mycobacterium tuberculosis (M. tuberculosis) is the causative agent of tuberculosis (TB), which continues to be a leading cause of death from infectious diseases globally. Lung epithelial cells play a crucial role in the infection process of M. tuberculosis. However, the specific M. tuberculosis proteins that regulate lung epithelial cells remain to be identified, and the mechanisms underlying the interaction between M. tuberculosis and lung epithelial cells are still not fully understood. Here, we found that the Rv0927c inhibits the proliferation of lung epithelial cells (line A549) both in vitro and in vivo. Flow cytometry analysis demonstrated that Rv0927c significantly increased apoptosis in A549 cells and led to a decrease in mitochondrial membrane potential. Additionally, Western blot analysis indicated that Rv0927c facilitated the cleavage of caspase-3, caspase-9, and PARP, while showing no effect on the cleavage level of caspase-8. Furthermore, Rv0927c interacts with host TUFM molecules, which is necessary for Rv0927c to inhibit apoptosis in host cells. Our findings provide evidence that Rv0927c inhibits proliferation and regulates apoptosis by targeting TUFM in A549 cells.