Deciphering the role of a unique methyltransferase in Mycobacterial infection

Abstract

Tuberculosis is a life threatening disease caused by the intracellular pathogen Mycobacterium tuberculosis (Mtb), resulting in around two million deaths annually worldwide. Mtb is known to have acquired certain features that help in establishing infection and persisting for longer durations in the host. Recent studies have revealed the acquisition of certain unique methyltransferases by Mtb as a function of phylogenetic evolution which points towards their potential involvement in mycobacterial pathogenesis. In the present study, we identified one such hypothetical methyltransferase (Rvxxxx) gene unique to Mtb complex i.e., absent in non‐pathogenic Mycobacteria. Our in‐silico analysis revealed that Rvxxxx gene possesses an S‐adenosylmethionine binding site and a methyltransferase domain, which was further confirmed through in vitro studies. The introduction of Rvxxxx in the genome of Mycobacterium smegmatis lead to significant perturbations in the physiological and morphological features of the bacilli as well as markedly enhanced its ability to resist and adapt to hostile conditions. Furthermore, recombinant M. smegmatis showed increase in infectivity and survival within host macrophages ex vivo. In addition, Rvxxxx was also found to modulate the proteome profile of recombinant M. smegmatis. Cumulatively, the results of this study indicate that the identified hypothetical methyltransferase Rvxxxx may play a significant role in Mtb pathogenesis and niche adaptation.Support or Funding InformationThe Council of Scientific and Industrial Research, Govt. of India