M.tb-Rv2462c of Mycobacterium tuberculosis Shows Chaperone-like Activity and Plays a Role in Stress Adaptation and Immunomodulation

SIMPLE SUMMARY: Mycobacterium tuberculosis protein tig (Rv2462c) is present in membrane fraction along with the cytosol. It has been previously reported to assist in the folding of nascent polypeptides. We have investigated the role of Mycobacterium tuberculosis tig in stress adaptation; for example, it exhibits roles in thermal and oxidative shock, survival within macrophages, biofilm formation and immunological responses. Our findings establish the contribution of tig to tolerance and adaptation to host-generated stresses, implying its involvement in the infection cycle of Mycobacterium tuberculosis. These attributes of Tig highlights its significance in Mycobacterium tuberculosis virulence and make it an important target for novel therapeutic interventions against tuberculosis. ABSTRACT: Mycobacterium tuberculosis (M.tb)-encoded factors protect it against host-generated stresses and support its survival in the hostile host environment. M.tb possesses two peptidyl-prolyl cis-trans isomerases and a probable trigger factor encoded by Rv2462c which has an FKBP-like PPIase domain. PPIases are known to assist the folding of peptidyl-prolyl bonds and are involved in various cellular processes important for bacterial survival in host-generated stresses. In this study, we aim to functionally characterize Rv2462c of M.tb. Our data suggest that the trigger factor of M.tb exhibits chaperone activity both in vitro and in vivo. Heterologous expression of M.tb-Rv2462c locus into Mycobacterium smegmatis enhanced its survival within macrophages, adaptation to oxidative stress and biofilm formation. M.tb-trigger factor has strong immunomodulatory potential and modifies the cytokine profile of the host towards the proinflammatory axis.