Overexpression of efflux pumps in Mycobacterium tuberculosis can contributes in drug resistance development

سال انتشار: 1399
نوع سند: مقاله کنفرانسی
زبان: انگلیسی
مشاهده: 241

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شناسه ملی سند علمی:

MEDISM21_005

تاریخ نمایه سازی: 23 مرداد 1400

چکیده مقاله:

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.

نویسندگان

Jalil Kardan-Yamchi

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

Hossein Kazemian

Department of Microbiology, Faculty of Medicine, Ilam University of Medical Sciences, Ilam. Iran

Hamid Reza Abtahi

Thoracic Research Center, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran

Sirus Amini

Tehran Regional Reference Laboratory for Tuberculosis, Tehran University of Medical Sciences, Tehran, Iran

Mohammad Mehdi Feizabadi

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