Efflux pump gene expression and efflux proteins in multidrug resistant mycobacterium tuberculosis complex

Isoniazid (INH) and rifampicin (RIF) are the most effective drugs in the treatment of tuberculosis. Known of molecular resistance mechanisms for these important tuberculosis drugs is essential to quick diagnoses of multidrug-resistant (MDR) tuberculosis and extensive drug-resistant tuberculosis. Numerous studies show efflux pump as an important mechanism for antibiotic resistance and using of efflux inhibitors with antituberculosis drugs during treatment, enhanced success. 40 clinical MDR Mycobacterium tuberculosis isolates and 40 clinical pan-sensitive isolates were included to evaluate the expression of 20 putative drug efflux pump (EP) genes and sequence mutations in rpoB (RIF), katG (INH), the inhA promoter (INH), and oxyR-ahpC (INH). Nine and three MDR isolates were induced to over- express efflux pump genes by INH and RIF, respectively. drrA, drrB, efpA, jefA, mmr, Rv0849, Rv1634, and Rv1250 were overexpressed under INH or RIF stress. MDR isolates that carried the wild-type katG, inhA, and oxyR-ahpC efflux pump genes were most overexpressed under INH stress in a than in those that carried mutations. Without drug inducement, efpA, Rv0849, Rv1250, Rv1634, Rv2994, stp, Rv2459, pstB, drrA, and drrB expression levels were significantly higher (P < 0.05) in 40 MDR isolates than in 40 pan- sensitive isolates. In conclusion, EP may play an important role in INH acquired resistance in MDR tuberculosis especially with mutations in katG and INH genes. Understanding of expression levels for EP genes between MDR and sensitive tuberculosis some may be helpful to diagnose and treat resistant tuberculosis.