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


OBJECTIVES: Thousands of cases of multi-drug resistant Mycobacteria tuberculosis (MTB) have been observed in the Philippines but studies on the genotypes that underlie the observed drug resistance profiles have been lacking. This study aimed to analyse whole genomes of clinical isolates of MTB representing varying 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 SNPs identification in genes reported to be associated with resistance against isoniazid, rifampicin, ethambutol, streptomycin, pyrazinamide, and fluoroquinolone.

RESULTS: The draft assemblies covered an average of 97.08% of the expected genome size. Seven out of ten isolates belonged to the Indo-Oceanic lineage/EA12 Manila clade. Two isolates were classified into Euro-American lineage, while the pre-XDR (pre-extremely drug resistant) isolate was classified under East Asian Beijing clade. The SNPs katG Ser315Thr, rpoB Ser450Leu, and embB Met306Val were found in isoniazid (4/7), rifampicin (3/6), and ethambutol-resistant samples (2/6), respectively, but not in susceptible isolates. Mutations in inhA promoter, pncA, and gyrA known to be involved in resistance against isoniazid, pyrazinamide, and fluoroquinolone respectively, were also identified.

CONCLUSIONS: This study represents the first effort to investigate whole genomes of Philippine clinical strains of MTB exhibiting various profiles of multi-drug resistance. Whole genome data can provide valuable insights to the mechanistic and epidemiological qualities of tuberculosis in a high burden setting such as the Philippines.

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