Overexpression of efflux pumps in Mycobacterium tuberculosis can contributes in drug resistance development
- سال انتشار: 1399
- محل انتشار: بیست و یکمین کنگره بین المللی میکروب شناسی ایران
- کد COI اختصاصی: MEDISM21_005
- زبان مقاله: انگلیسی
- تعداد مشاهده: 253
نویسندگان
Division of Microbiology, Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran, Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Department of Microbiology, Faculty of Medicine, Ilam University of Medical Sciences, Ilam. Iran
Thoracic Research Center, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
Tehran Regional Reference Laboratory for Tuberculosis, Tehran University of Medical Sciences, Tehran, Iran
Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran, Thoracic Research Center, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
چکیده
Background and Aim : Active extrusion of anti-tuberculosis drugs via efflux pumps (EPs) has been considered as an alternative mechanism for drug resistance in Mycobacterium tuberculosis. Expression of drug efflux transporters in a series of drug-susceptible/resistant M. tuberculosis isolates was investigated in the present study.Methods : Thirty-one M. tuberculosis isolates were studied. Drug susceptibility testing of rifampicin and isoniazid was performed using proportion method. The cDNA was synthesized from extracted RNA and expression analysis of ۱۴ efflux pumps genes was evaluated by real-time quantitative reverse transcriptase PCR. Minimum inhibitory concentrations (MICs) of rifampicin and isoniazid were evaluated with and without of an EPs inhibitor, carbonyl cyanide ۳-chlorophenylhydrazone (CCCP).Results : Among the ۲۱ drug-resistant isolates were detected, ۱۴ were over expressed (> ۴ fold) in at least one of the efflux pumps genes. The drrA, Rv۱۲۱۸c, and Rv۱۴۱۰c were found to be the most commonly overexpressed, being in ۷ isolates followed by stp and Rv۱۲۷۳c in ۵ and ۴ isolates, respectively. However, no elevation was observed in the expression of mmr, Rv۱۲۵۰, Rv۱۶۳۴ and Rv۱۲۵۸c genes in any of the isolates. MICs of rifampicin, but not isoniazid, were decreased from ۲ to ۸ folds in the presence of CCCP.Conclusion : Overexpression of EP genes can contribute in the development of resistant-phenotypes in M. tuberculosis strains. Inhibition of efflux transporters can provide a promising target for drug discovery and improve tuberculosis treatment.کلیدواژه ها
Mycobacterium tuberculosis, Drug resistance, Efflux pumps, Expression, CCCPاطلاعات بیشتر در مورد COI
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