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Title: Whole-genome sequencing analysis of serially isolated multi-drug and extensively drug resistant Mycobacterium tuberculosis from Thai patients
Authors: Kiatichai Faksri
Jun Hao Tan
Areeya Disratthakit
Eryu Xia
Therdsak Prammananan
Prapat Suriyaphol
Chiea Chuen Khor
Yik Ying Teo
Rick Twee Hee Ong
Angkana Chaiprasert
Khon Kaen University
National University of Singapore
Mahidol University
NUS Graduate School for Integrative Sciences and Engineering
Thailand National Center for Genetic Engineering and Biotechnology
A-Star, Genome Institute of Singapore
Keywords: Agricultural and Biological Sciences;Biochemistry, Genetics and Molecular Biology
Issue Date: 1-Aug-2016
Citation: PLoS ONE. Vol.11, No.8 (2016)
Abstract: © 2016 Faksri et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Multi-drug and extensively drug-resistant tuberculosis (MDR and XDR-TB) are problems that threaten public health worldwide. Only some genetic markers associated with drugresistant TB are known. Whole-genome sequencing (WGS) is a promising tool for distinguishing between re-infection and persistent infection in isolates taken at different times from a single patient, but has not yet been applied in MDR and XDR-TB. We aim to detect genetic markers associated with drug resistance and distinguish between reinfection and persistent infection from MDR and XDR-TB patients based on WGS analysis. Samples of Mycobacterium tuberculosis (n = 7), serially isolated from 2 MDR cases and 1 XDR-TB case, were retrieved from Siriraj Hospital, Bangkok. TheWGS analysis used an Illumina Miseq sequencer. In cases of persistent infection, MDR-TB isolates differed at an average of 2 SNPs across the span of 2-9 months whereas in the case of reinfection, isolates differed at 61 SNPs across 2 years. Known genetic markers associated with resistance were detected from strains susceptible to streptomycin (2/7 isolates), p-aminosalicylic acid (3/7 isolates) and fluoroquinolone drugs. Among fluoroquinolone drugs, ofloxacin had the highest phenotype-genotype concordance (6/7 isolates), whereas gatifloxcain had the lowest (3/7 isolates). A putative candidate SNP in Rv2477c associated with kanamycin and amikacin resistance was suggested for further validation. WGS provided comprehensive results regarding molecular epidemiology, distinguishing between persistent infection and reinfection in M/XDR-TB and potentially can be used for detection of novel mutations associated with drug resistance.
ISSN: 19326203
Appears in Collections:Scopus 2016-2017

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