Evolution and spread of a highly drug resistant strain of Mycobacterium tuberculosis in Papua New Guinea

Autor: Arnold Bainomugisa, Evelyn Lavu, Sushil Pandey, Suman Majumdar, Jennifer Banamu, Chris Coulter, Ben Marais, Lachlan Coin, Stephen M. Graham, Philipp du Cros
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: BMC Infectious Diseases, Vol 22, Iss 1, Pp 1-15 (2022)
Druh dokumentu: article
ISSN: 1471-2334
DOI: 10.1186/s12879-022-07414-2
Popis: Abstract Background Molecular mechanisms determining the transmission and prevalence of drug resistant tuberculosis (DR-TB) in Papua New Guinea (PNG) are poorly understood. We used genomic and drug susceptibility data to explore the evolutionary history, temporal acquisition of resistance and transmission dynamics of DR-TB across PNG. Methods We performed whole genome sequencing on isolates from Central Public Health Laboratory, PNG, collected 2017–2019. Data analysis was done on a composite dataset that also included 100 genomes previously sequenced from Daru, PNG (2012–2015). Results Sampled isolates represented 14 of the 22 PNG provinces, the majority (66/94; 70%) came from the National Capital District (NCD). In the composite dataset, 91% of strains were Beijing 2.2.1.1, identified in 13 provinces. Phylogenetic tree of Beijing strains revealed two clades, Daru dominant clade (A) and NCD dominant clade (B). Multi-drug resistance (MDR) was repeatedly and independently acquired, with the first MDR cases in both clades noted to have emerged in the early 1990s, while fluoroquinolone resistance emerged in 2009 (95% highest posterior density 2000–2016). We identified the presence of a frameshift mutation within Rv0678 (p.Asp47fs) which has been suggested to confer resistance to bedaquiline, despite no known exposure to the drug. Overall genomic clustering was significantly associated with rpoC compensatory and inhA promoter mutations (p
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