Mycobacterium tuberculosis PE13 (Rv1195) manipulates the host cell fate via p38-ERK-NF-κB axis and apoptosis

PE/PPE family proteins are mycobacteria unique molecules, named after their N-terminal conserved PE (Pro-Glu) and PPE (Pro-Pro-Glu) domains. Mycobacterium tuberculosis (Mtb) PE family gene encoded cell surface proteins are previously reported to be involved in virulence and interaction with host. To explore the role of a novel PE member (PE13, Rv1195), M. smegmatis was used as surrogate host. The study showed that Rv1195 was a cell wall associated protein. Rv1195 can enhance the survival of recombinants under stress conditions such as H2O2, SDS, low pH. This is largely due to the upregulated transcription of Rv1195, since diverse stresses can increase the promoter activity of Rv1195 gene, consistent with enhanced survival within macrophages. Ms_Rv1195 infection also increased the production of interlukin-6 (IL-6) and IL-1 beta from macrophages, while decreased the secretion of suppressor of cytokine signaling 3 (SOCS3) in comparison with the vector-only control. The cell death was also precipitated by the Ms_Rv1195 infection. Inhibitors treatment showed that the p38-ERK-NF-kappa B axis was involved in the Rv1195 triggered change of IL-6 and IL-1 beta expression. In summary, we showed that PE13 (Rv1195) is a new PE family member actively engaged in the interaction between Mycobacterium and host, signaling through p38-ERK-NF-kappa B axis and apoptosis.