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

• Published in: Infection, genetics and evolution Vol. 36; pp. 23 - 26
• Main Authors: Kardan Yamchi, Jalil, Haeili, Mehri, Gizaw Feyisa, Seifu, Kazemian, Hossein, Hashemi Shahraki, Abdolrazagh, Zahednamazi, Fatemeh, Imani Fooladi, Abbas Ali, Feizabadi, Mohammad Mehdi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-12-2015
• Subjects: Antitubercular Agents - pharmacology; Drug Resistance, Bacterial - genetics; Efflux pump; Gene Expression; Genes, Bacterial; Humans; Iran - epidemiology; M. tuberculosis; Microbial Sensitivity Tests; Mutation; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - genetics; qRT-PCR; Tuberculosis - epidemiology; Tuberculosis - microbiology; Tuberculosis, Multidrug-Resistant - epidemiology; Tuberculosis, Multidrug-Resistant - microbiology; Iran; M. tuberculosis; Efflux pump; qRT-PCR
• ISSN: 1567-1348; 1567-7257
• DOI: 10.1016/j.meegid.2015.08.036

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.
•Evaluation of efflux pump gene expression among drug susceptible and drug resistant isolates of Mycobacterium tuberculosis•12 of 21 drug resistant isolates were over-expressed (>4 fold) at least in one of the studied efflux pumps•5 of 7 isolates without any mutation in katG, inhA and rpoB genes, showed an elevation in expression level of efflux pumps