MDR TB WGS sequencing

Tuberculosis (Tb) represents a major health issue with an estimation of 10.4 million new cases each year (1). The spread of multidrug resistant (MDR) strains of Mycobacterium tuberculosis (Mtb) resistant to at least rifampicin (RIF) and isoniazid (INH) is of global concern. Among the clinical Mtb isolates collected at the French NRC for Mycobacteria (CNR MyRMA), we observed a cluster of MDR isolates displaying a striking combination of 2 mutations encoding resistance to RIF and INH, which modify important redox functions: KatG-A110V enhances the catalase-peroxydase activity, and EthA-Q269* abolishes the monooxygenase activity (2, 3). We showed by MIRU-VNTR typing that these isolates, which mostly originated from the Congo area, were closely related (2). The aim of our project is to characterize at the genome level the molecular adaptation of this peculiar clone which has recently spread in the Congo area and displays a very unusual combination of drug resistance mutations altering enzymatic functions