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

Journal Article · · Journal of Global Antimicrobial Resistance
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  1. Univ. of the Philippines, Diliman, Quezon City (Philippines)
  2. Univ. of the Philippines, Ermita, Manila (Philippines)
  3. Univ. of California, San Francisco, CA (United States)
  4. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  5. Univ. of the Philippines, Diliman, Quezon City (Philippines); Univ. of the Philippines, Ermita, Manila (Philippines)
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. 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). 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. 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.
Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC)
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1567152
Journal Information:
Journal of Global Antimicrobial Resistance, Journal Name: Journal of Global Antimicrobial Resistance Journal Issue: C Vol. 15; ISSN 2213-7165
Publisher:
Elsevier - The International Society of ChemotherapyCopyright Statement
Country of Publication:
United States
Language:
English

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