Evaluation of efflux pump gene expression among drug susceptible and drug resistant strains of Mycobacterium tuberculosis from Iran

Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases
Jalil Kardan YamchiMohammad Mehdi Feizabadi

Abstract

Absence of mutations within the genes encoding drug targets in some phenotypically drug resistant strains of Mycobacterium tuberculosis suggests possible involvement of alternative mechanisms such as over-expression of efflux pumps. We investigated the expression level of Rv1410c, Rv2459, Rv1218c and Rv1273c efflux pumps gene by real-time quantitative reverse transcription PCR (qRT-PCR) in 31 clinical isolates of M. tuberculosis. Susceptibility to first-line drugs was performed using the proportion method. Twenty one isolates were characterized with drug resistance (DR), and among them 12 showed a significantly elevated level of expression (>4 fold) for at least one of the studied genes encoding for efflux pumps. Point mutations in the katG (codons 315 or 335) and rpoB (codons 456 and 441) genes were found in 42.85% and 66.6% of drug resistant isolates, respectively. Only one isolate showed mutation at position -15 of the inhA promoter region. Among the 7 isolates (33.33%) which had no mutation in the studied regions of drug target genes, 5 isolates showed over-expression for efflux pumps. Our results demonstrated that over-expression of efflux pumps can contribute to drug resistance in M. tuberculosis.

References

Jan 24, 2006·Biochemical Pharmacology·Olga Lomovskaya, Keith A Bostian
Mar 7, 2008·Microbial Drug Resistance : MDR : Mechanisms, Epidemiology, and Disease·Xin JiangHonghai Wang
Aug 30, 2011·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Liliana RodriguesMiguel Viveiros
Oct 16, 2015·The International Journal of Tuberculosis and Lung Disease : the Official Journal of the International Union Against Tuberculosis and Lung Disease·Y Zhang, W-W Yew

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Citations

May 8, 2020·Microbial Drug Resistance : MDR : Mechanisms, Epidemiology, and Disease·Ana Laura Granados-TristánKatia Peñuelas-Urquides
May 11, 2017·Frontiers in Microbiology·Mohammad J NasiriMohammad M Feizabadi
Jan 23, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Lady Laura Del Rio OsorioCarlos David Grande-Tovar

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