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

## TL;DR

This study shows that a protein from tuberculosis bacteria, Rv0927c, stops lung cells from growing and causes them to die by targeting a specific host molecule.

## Contribution

The novel contribution is identifying Rv0927c as a tuberculosis protein that induces apoptosis in lung epithelial cells via interaction with mitochondrial TUFM.

## Key findings

- Rv0927c inhibits the proliferation of A549 lung epithelial cells in vitro and in vivo.
- Rv0927c promotes intrinsic apoptosis by cleaving caspase-3, caspase-9, and PARP, and reducing mitochondrial membrane potential.
- Rv0927c interacts with host TUFM, and this interaction is essential for inducing apoptosis.

## Abstract

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.

In this study, CCK8 assay and xenograft tumor models were employed to investigate the effect of M. tuberculosis protein Rv0927c on the proliferation of lung epithelial cells (line A549). Flow cytometry was used to detect cell apoptosis, Western blot analysis was performed to examine the cleavage levels of apoptosis-related proteins, and JC-1 staining assay was conducted to assess mitochondrial membrane potential. Additionally, the interaction between Rv0927c and host TUFM molecules was verified by immunoprecipitation, and the role of this interaction in Rv0927c-induced apoptosis was also explored.

The results showed that Rv0927c inhibits the proliferation of lung epithelial cells both in vitro and in vivo. Flow cytometry analysis demonstrated that Rv0927c significantly increased apoptosis in A549 cells. Additionally, Rv0927c facilitated the cleavage of caspase-3, caspase-9, and PARP, while having no effect on the cleavage level of caspase-8, and it led to a decrease in mitochondrial membrane potential. Furthermore, Rv0927c interacts with host TUFM molecules, which is necessary for Rv0927c to promote apoptosis in host cells.

Our findings provide evidence that Rv0927c inhibits proliferation and regulates apoptosis by targeting TUFM in A549 cells, which contributes to the understanding of the mechanisms underlying the interaction between M. tuberculosis and lung epithelial cells.