Mycobacterium tuberculosis Rv1324 Protein Contributes to Mycobacterial Persistence and Causes Pathological Lung Injury in Mice by Inducing Ferroptosis

Abstract

The intracellular survival of M. tuberculosis (Mtb) plays a crucial role in its pathogenesis, which depends on various Mtb oxidoreductases that are resistant to reactive oxygen and nitrogen species (ROS and RNS) that are generated by the host during Mtb infection. Secretory protein Rv1324 is a potential virulence factor of Mtb and is a possible thioredoxin that has oxidoreductase activity against ROS and RNS during Mtb infection. We investigated the biochemical properties of Mtb Rv1324 and its role in mycobacterial survival and virulence. It was confirmed that the Rv1324 protein had antioxidant activity and an increased mycobacterial resistance to ROS and RNS. In addition, Rv1324 enhanced mycobacterial persistence and induced pathological injury and inflammation in the lungs of mice by activating ferroptosis. This study advances our understanding of the mechanisms of mycobacterial survival and pathogenesis, and it reveals a novel target for TB treatment.