Mutation analysis for detection of drug resistance in mycobacterium tuberculosis isolates from Khyber Pakhtunkhwa, Pakistan

To examine the frequency and distribution of mutations in the 'hot spot regions' of drug-resistant genes. The study was conducted at Provincial Tuberculosis Reference Laboratory, Peshawar, Pakistan, from April 2015 to March 2016, and comprised sputum samples. Isolates were tested for drug...

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Bibliographic Details
Published in:Journal of the Pakistan Medical Association 2017-11, Vol.67 (11), p.1684-1688
Main Authors: Ahmad, Bashir, Idrees, Muhammad, Ahmad, Kafeel, Bashir, Shumaila, Ahmad, Sajjad, Lin-Fang, Huang
Format: Article
Language:English
Subjects:
Analysis
Anopheles
Antitubercular Agents - pharmacology
Cohort Studies
DNA Mutational Analysis
DNA, Bacterial - genetics
Drug Resistance, Multiple, Bacterial - genetics
Drug therapy
Ethambutol
Genes
Humans
Microbial drug resistance
Microbial Sensitivity Tests
Mutation - genetics
Mycobacterium tuberculosis - drug effects
Mycobacterium tuberculosis - genetics
Pakistan - epidemiology
Rifampin
Tuberculosis
Tuberculosis, Multidrug-Resistant - epidemiology
Tuberculosis, Multidrug-Resistant - microbiology
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Summary:To examine the frequency and distribution of mutations in the 'hot spot regions' of drug-resistant genes. The study was conducted at Provincial Tuberculosis Reference Laboratory, Peshawar, Pakistan, from April 2015 to March 2016, and comprised sputum samples. Isolates were tested for drug susceptibility and resistant isolates were investigated for mutations analysis in the 'hot spot regions' of rpoB, rpsL, embB, pncA, gyrA and gyrB genes. Of the 163 isolates, 47(28.8%) isolates were resistant to streptomycin, 56(34.36%) to rifampicin, 31(19%) to ethambutol, 16(9.82%) to pyrazinamide and 59(36.2%) isolates were resistant to ofloxacin. Resistant isolates were randomly selected for mutation analysis. Moreover, 14(25%) rifampicin-resistant isolates were analyed for mutation in rpoB gene. Ser450Leu, Asp435Gly, Ser450Gln, Gly455Asp and Pro454His mutations were detected in the selected isolates. Furthermore, 16(34%) streptomycin-resistant isolates were analysed for mutation in rpsL gene. Lys43Arg, Lys88Arg and Lys111Ile mutations were detected in rpsL gene of 6(37.5%) isolates. Besides, 16(51.6%) ethambutol-resistant isolates were analysed for mutations in embB mutation; Ala281val, Met306Leu and Met306Val mutations were detected in 10(10(62.5%) isolates. Also, 8(50%) pyrazinamide-resistant isolates were analysed for mutation in pncA gene. Some novel mutations were found in rpoB, rpsL and pncA genes.
ISSN:0030-9982