Evaluation of Different Drugs in Down-Regulation of Efflux Pump Genes expression in Methicillin-Resistant Staphylococcus aureus Strains

Abstract

Antimicrobial resistance caused by efflux systems is not widely studied in Staphylococcus aureus. In the present study, prevalence of NorA and NorB efflux pumps was studied in thirteen Methicillin-Resistant Staphylococcus aureus (MRSA) strains using a pair of primers with Polymerase Chain Reaction (PCR). Antibiotic susceptibility study in NorA and NorB efflux positive isolates was carried out according to the Clinical and Laboratory Standards Institute guidelines. To evaluate the effects of various drugs at half of their MIC on NorA and NorB efflux pump, expression of NorA and NorB genes was measured through semi-quantitative PCR. Our results demonstrated that out of 13 MRSA strains, 8 strains were both NorA and NorB positive and 2 strains were NorA positive. Susceptibility data revealed that Vancoplus appeared to be the most active antibacterial against NorA and NorB efflux pumps positive MRSA strains with MIC values 0.25 to 0.5 µg mL^-1. The second most active antibacterial agent was teicoplanin with MIC values 0.5 to 1 µg mL^-1. The MICs of vancomycin and daptomycin ranged from 32 to 64 µg mL^-1. Treatment of MRSA strains possessing NorA and NorB efflux pumps with Vancoplus caused significant down-regulation of the expression of NorA and NorB genes (P<0.001) as compared to the control (without treatment) whereas other drugs such as vancomycin, linezolid, teicoplanin and daptomycin failed to produce any significant changes in the expression of these genes (P>0.05). From the above results, it can be concluded that Vancoplus (vancomycin+ceftriaxone+VRP1020) can be one of the best options to treat infections caused by MRSA possessing NorA and NorB efflux pumps.