The number of multidrug-resistant strains of continues to increase， and new strategies for the treatment of associated infections are necessary. Recently， numerous studies have shown that efflux pumps (EPs) play key roles in universal bacterial mechanisms that contribute to antibiotic resistance. In addition， studies have shown that the effects of antibiotics that are subjected to efflux can be reinforced by their combined use with efflux pump inhibitors (EPIs). Unfortunately， the role of the efflux system in remains barely understood. In this study， we evaluated the role of EPs and resistance genes in the resistance generated by clinical strains of to antibiotics. A set of 10 strains were charact... More
The number of multidrug-resistant strains of continues to increase， and new strategies for the treatment of associated infections are necessary. Recently， numerous studies have shown that efflux pumps (EPs) play key roles in universal bacterial mechanisms that contribute to antibiotic resistance. In addition， studies have shown that the effects of antibiotics that are subjected to efflux can be reinforced by their combined use with efflux pump inhibitors (EPIs). Unfortunately， the role of the efflux system in remains barely understood. In this study， we evaluated the role of EPs and resistance genes in the resistance generated by clinical strains of to antibiotics. A set of 10 strains were characterized by drug resistance， associated resistance genes， and antibiotic profiles in the presence and absence of EPIs. Efflux activity was studied on a real time basis through a fluorometric method. Quantification of the levels of mRNA transcription of efflux pump genes (EPGs) was determined by RT-qPCR. Several approaches (detection of resistance genes， drug susceptibility testing， and growth kinetics analysis) were used to assess the correlation between the effect of the EPIs and the resistance levels. Analysis of the growth inhibition tests showed that the antibiotic activity was enhanced by the synergy of EPIs. Among the various resistance genes that confer antibiotic resistance， different minimum inhibitory concentrations (MICs) were observed. The different levels of resistance were reduced by EPIs. Real time fluorometry showed that all the strains presented inherent efflux activity， conferring varying levels of inhibition in the presence of EPIs. Moreover， 15 EPGs were overexpressed in the presence of antibiotics. The addition of EPIs to antibiotics led to downregulation in the expression of some EPGs and a simultaneous increase in drug resistance and sensitivity. These results demonstrated the contribution of these EPs in the resistant phenotype of the clinical strains of that are under investigation， independently of the resistant genotype of the respective strains. Intrinsic efflux activity was possibly linked to the evolution of resistance in multidrug-resistant isolates of . Furthermore， the inhibition of EPs by EPIs could enhance the clinical effects of antibiotics.
