Mycolic acid biosynthesis and processing in Mycobacterium tuberculosis

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The tuberculosis-causing, human pathogen Mycobacterium tuberculosis (MTB) contains a lipid rich ‘waxy‘ cell wall that forms a protective barrier against harsh environments. Mycobacterial lipids not only offer a protective cover, but are also involved in interactions with infected host cells. Furthermore, some lipid components are essential for the survival of MTB and thus the enzymes that catalyze their biosynthesis represent potential targets for antimycobacterial drugs. The proposed project aims to further our understanding about how these lipid building blocks are made by generating defined mutants of MTB in candidate genes. The mutant strains will then be tested for loss of lipid components and/or accumulation of intermediate compounds. The study also aims to assess the role of specific lipids in virulence by testing these mutant strains in laboratory models of infection. The hope is that these studies will aid in our search not only for new drugs effective against tuberculosis, but also a better vaccine.