Whole Genome Sequencing Based Characterization of Extensively Drug-Resistant Mycobacterium tuberculosis Isolates from Pakistan

• DOI: 10.1371/journal.pone.0117771
• Publication Date: 2015-02-26T18:47:11Z
• Authors: Asho Ali; Zahra Hasan; Ruth McNerney; Kim Mallard; Grant Hill-Cawthorne; Francesc Coll; Mridul Nair; Arnab Pain; Taane G. Clark; Rumina Hasan
• Keywords: Extensively drug-resistant tuberculosis

Improved molecular diagnostic methods for detection drug resistance in Mycobacterium tuberculosis (MTB) strains are required. Resistance to first- and second- line anti-tuberculous drugs has been associated with single nucleotide polymorphisms (SNPs) particular genes. However, these SNPs can vary between MTB lineages therefore local data is required describe different strain populations. We used whole genome sequencing (WGS) characterize 37 extensively drug-resistant (XDR) isolates from Pakistan investigated 40 genes resistance. Rifampicin was attributable the rpoB hot-spot region. Isoniazid most commonly katG codon 315 (92%) mutation followed by inhA S94A (8%) however, one did not have katG, or oxyR-ahpC. All were pyrazimamide resistant but only 43% had pncA SNPs. Ethambutol predominantly embB 306 (62%) mutations, additional at codons 406, 378 328 also present. Fluoroquinolone gyrA 91–94 81% of strains; four gyrB while others either gyrB. Streptomycin mutations ribosomal RNA genes; rpsL 43 (42%); rrs 500 region (16%), gidB (34%) six any Amikacin/kanamycin/capreomycin nt1401 (78%) nt1484 (3%), except seven (19%) strains. estimate that if common targets current commercial assays used, concordance phenotypic genotypic testing XDR would rifampicin (100%), isoniazid (92%), flouroquinolones (81%), aminoglycoside ethambutol (62%); provide less than half isolates. This work highlights importance expanded