Multi-clonal evolution of MDR/XDRM. tuberculosisin a high prevalence setting in Papua New Guinea over three decades

Abstract

An outbreak of multi-drug resistant tuberculosis has been reported on Daru Island, Papua New Guinea. The Mycobacterium tuberculosis strains driving this outbreak and the temporal accrual of drug resistance mutations have not been described. We analyzed 100 isolates using whole genome sequencing and found 95 belonged to a single modern Beijing strain cluster. Molecular dating suggested acquisition of streptomycin and isoniazid resistance in the 1960s, with virulence potentially enhanced by a mycP1 mutation. The outbreak cluster demonstrated a high degree of co-resistance between isoniazid and ethionamide (80/95; 84.2%) attributed to an inhA promoter mutation combined with inhA and ndh coding ..