Abstract
An outbreak of multi-drug resistant (MDR) tuberculosis (TB) has been reported on Daru Island, Papua New Guinea. Mycobacterium tuberculosis strains driving this outbreak and the temporal accrual of drug resistance mutations have not been described. Whole genome sequencing of 100 of 165 clinical isolates referred from Daru General Hospital to the Supranational reference laboratory, Brisbane, during 2012–2015 revealed that 95 belonged to a single modern Beijing sub-lineage strain. Molecular dating suggested acquisition of streptomycin and isoniazid resistance in the 1960s, with potentially enhanced virulence mediated by an mycP1 mutation. The Beijing sub-lineage strain 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 mutations. Multi-drug resistance, observed in 78/95 samples, emerged with the acquisition of a typical rpoB mutation together with a compensatory rpoC mutation in the 1980s. There was independent acquisition of fluoroquinolone and aminoglycoside resistance, and evidence of local transmission of extensively drug resistant (XDR) strains from 2009. These findings underline the importance of whole genome sequencing in informing an effective public health response to MDR/XDR TB.
Highlights
An estimated 10.4 million cases of tuberculosis (TB) occurred in 2015 and TB caused by Mycobacterium tuberculosis (MTB) was the leading cause of death from a single infectious agent [1]
MIRU-24 and Whole genome sequencing (WGS) were performed to understand the genetic diversity of circulating strains, reveal the mutations associated with drug resistance and explore the evolution of these mutations
Analysis of SNPs derived from WGS revealed all the strains in the dominant cluster formed a monophyletic clade in the East-Asian lineage, while all the remaining strains belonged to the Euro-American lineage (Fig. S2)
Summary
An estimated 10.4 million cases of tuberculosis (TB) occurred in 2015 and TB caused by Mycobacterium tuberculosis (MTB) was the leading cause of death from a single infectious agent [1]. The emergence and spread of drug-resistant MTB strains pose a major challenge to global TB prevention efforts [2]. Multi-drug-resistant (MDR) TB, which is resistant to at least isoniazid and rifampicin, accounted for an estimated 480 000 new cases and 250 000 deaths in 2015 [1]. In MTB, drug resistance occurs mainly due to the accumulation of chromosomal resistanceconferring mutations without evidence of lateral gene transfer [4]. The emergence of drug resistance is dependent on the rate of acquisition of resistance-conferring mutations and the frequency with which these drug-resistant strains are transmitted, especially in communities with inadequate treatment or poor adherence to treatment [5, 6].
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