Characterization of a novel Mycobacterium tuberculosis serine protease Rv1815 in regulating bacterial metabolism and macrophage intracellular survival

The serine proteases of Mycobacterium tuberculosis (Mtb) are critical contributors to bacterial invasion and pathogenesis. In this study, we characterized the role of a novel serine protease, the Rv1815 protein, in Mtb by purifying Rv1815 in Escherichia coli and constructing a rv1815 deletion mutant in Mtb. Our findings indicate that Rv1815 exhibits serine protease activity, can be secreted extracellularly, and is localized within the cytoplasm of macrophages. Furthermore, through proteomic analysis, we discovered that rv1815 is essential for the expression of proteins associated with bacterial virulence, survival, metabolism, and antibiotic resistance. Rv1815 promotes intracellular survival of Mtb in macrophages, enhances in vitro bacterial growth, and influences bacterial morphology. Additionally, Rv1815 negatively regulates Mtb's resistance to rifampicin. This study suggests that Rv1815 may play a significant role in the physiology and virulence of Mtb, providing novel insights into the relationship between mycobacterial serine protease and pathogenesis.