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Whole-genome sequencing and single nucleotide polymorphisms in multidrug-resistant clinical isolates of Mycobacterium tuberculosis from the Philippines.

Abstract：

OBJECTIVES:Thousands of cases of multidrug-resistant tuberculosis (TB) have been observed in the Philippines, but studies on the Mycobacterium tuberculosis (MTB) genotypes that underlie the observed drug resistance profiles are lacking. This study aimed to analyse the whole genomes of clinical MTB isolates representing various resistance profiles to identify single nucleotide polymorphisms (SNPs) in resistance-associated genes. METHODS:The genomes of ten MTB isolates cultured from banked sputum sources were sequenced. Bioinformatics analysis consisted of assembly, annotation and SNP identification in genes reported to be associated with resistance to isoniazid (INH), rifampicin (RIF), ethambutol (ETH), streptomycin, pyrazinamide (PZA) and fluoroquinolones (FQs). RESULTS:The draft assemblies covered an average of 97.08% of the expected genome size. Seven of the ten isolates belonged to the Indo-Oceanic lineage/EA12-Manila clade. Two isolates were classified into the Euro-American lineage, whilst the pre-XDR (pre-extensively drug-resistant) isolate was classified under the East Asian/Beijing clade. The SNPs katG Ser315Thr, rpoB Ser450Leu and embB Met306Val were found in INH- (4/7), RIF- (3/6) and ETH-resistant (2/6) isolates, respectively, but not in susceptible isolates. Mutations in the inhA promoter and in the pncA and gyrA genes known to be involved in resistance to INH, PZA and FQs, respectively, were also identified. CONCLUSIONS:This study represents the first effort to investigate the whole genomes of Philippine clinical strains of MTB exhibiting various multidrug resistance profiles. Whole-genome data can provide valuable insights to the mechanistic and epidemiological qualities of TB in a high-burden setting such as the Philippines.

journal_name

J Glob Antimicrob Resist

journal_title

Journal of global antimicrobial resistance

authors

Roa MB,Tablizo FA,Morado EKD,Cunanan LF,Uy IDC,Ng KCS,Manalastas-Cantos KG,Reyes JM,Ganchua SKC,Ang CF,Kato-Maeda M,Cattamanchi A,Karaoz U,Destura RV,Lluisma AO

doi

10.1016/j.jgar.2018.08.009

subject

Has Abstract

pub_date

2018-12-01 00:00:00

pages

239-245

eissn

2213-7165

issn

2213-7173

pii

S2213-7165(18)30156-5

journal_volume

15

pub_type

杂志文章

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