Mycobacterium tuberculosis m4C DNA methyltransferase Rv3204 promotes mycobacteria survival under oxidative stress

ROS can damage cellular components and is a key player in many cellular signaling. Tuberculosis remains a major global public health concern largely due to the ability of its causative agent-Mycobacterium tuberculosis (Mtb) to subvert ROS toxicity. DNA methylation deficiency was previously shown to attenuate the Mtb virulence. But the role of DNA methyltransferase in Mycobacteria survival and the link with ROS are unknown. Mycobacterial protein Rv3204 is a DNA methyltransferase specific for N4-methylcytosine instead of N6-methyladenine (m6A) or 5-methylocytosine (m5C). The survival rate of m4C methyltransferase deletion mutants was lowered, accompanied by higher accumulation of ROS and failure of upregulating the transcription of gene engaged in ROS clearance upon rifampin(Rif) exposure. Overall design: mRNA profiles of M.smegmatis overexpression strains WT and Ms_1939 by deep sequencing, using Illumina GAIIx