Coordinated Interaction Between Lon Protease and Catalase-peroxidase Regulates Virulence and Oxidative Stress Management During Salmonellosis

This study investigates the interplay between Lon protease and catalase-peroxidase (KatG) in relation to virulence modulation and the response to oxidative stress in Typhimurium (ST). Proteomic comparison of ST wild-type and deletion mutant led to the recognition of a highly expressed KatG protein product among five other protein candidates that were significantly affected by deletion. By employing a bacterium two-hybrid assay (B2H), we demonstrated that the catalytic domain of Lon protease potentially interacts with the KatG protein that leads to proteolytic cleavage. Assessment of virulence gene expression in single and double and mutants revealed to be a potential positive modulator of both pathogenicity Island-1 (SPI-1) and -2, while significantly affected SPI-1 genes. ST double deletion mutant, ∆ was more susceptible to survival defects within macrophage-like cells and exhibited meager colonization of the mouse spleen compared to the single deletion mutants. The findings reveal a previously unknown function of Lon and KatG interaction in virulence. Taken together, our experiments demonstrate the importance of Lon and KatG to cope with oxidative stress, for intracellular survival and virulence of .