Because of the lengthy anti-tubercular therapy and the increasing spread of drug-resistant Mycobacterium tuberculosis strains, the introduction of new anti-tubercular drugs and understanding of their mechanism of action is a global health priority. MmpL3 is one of the 13 large mycobacterial membrane proteins, responsible for mycolic acid transport and essential both in vitro and in vivo. During the last decade, several chemical scaffolds inhibiting MmpL3 have been identified, making this protein a promiscuous but relevant cellular target. Here we aim to study a new molecule that is thought to inhibit MmpL3 and that is highly potent against the tubercular pathogen. In particular we will analyze the whole genome of spontaneous mutant strains of M. tuberculosis resistant to this molecule, towards a better understanding of its mechanism of action.
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