Mycolic Acid like lipids act as substrates forMycobacterium tuberculosis melH

Mycobacterium tuberculosis(Mtb), the pathogenic bacterium that causes tuberculosis, has developed its own ways of evading defense mechanisms to counteract the lethal effects of reactive oxygen species (ROS) generated within the host macrophages during infection. ThemelHgene present inMtbandMycobacterium marinum(Mm) plays an important role to reduce ROS generated during infection. ThemelHgene encodes for an epoxide hydrolase. Bioinformatics data suggests that encoded enzyme utilizes lipid substrates for its function. Initially, we used a lipid fractionation approach coupled with liquid chromatography mass spectrometry (LC-MS) and treatment with active MelH enzyme to identify potential substrates for MelH. We found classes of mycolic acids, predominantly epoxy mycolic acids accumulate in themelHmutant and upon treatment with MelH are reduced in the lipid fraction. These results provide insight into how MelH encoded in themel2operon contributes toMtbvirulence and persistence and present further evidence for potential mechanisms of action if MelH is targeted for antitubercular drug discovery.