Differential contribution of acrab and oqxab efflux pumps to multidrug resistance in clinical isolates of Klebsiella pneumoniae

Infections caused by multidrug-resistant K. pneumoniae characterize a major warning throughout the world owing to enhanced mortality and treatment limitations. Efflux pumps have an important role as a mechanism of antibiotic resistance in K. pneumoniae. To investigate the efflux-mediated resistance mechanisms of K. pneumoniae, the expression of efflux pump genes (acrA, acrB, oqxA and oqxB) and pump regulators (marA, soxS and rarA) were examined by quantitative real-time PCR. Efflux pump inhibitor CCCP was able to a reduce MIC values of ciprofloxacin by 2- to 64-fold in 43/46 (93%) in MDR-K. pneumoniae isolates. Compared to the reference strain (strain A111), acrA and acrB overexpression were observed in 34 (74%) and 37 (81%), respectively in ciprofloxacin-resistant isolates. Interestingly oqxA overexpression was observed in 34 (74%) ciprofloxacin resistant isolates and oqxB was observed in 24 (53%) ciprofloxacin resistant isolates. High expression levels of regulators MarA, soxS and rarA were also detected in 23 (50%), 24 (53%) and 28 (61%), respectively in ciprofloxacin resistant isolates. Additionally, there were a moderate correlation between the expression of acrAB and marA (r = 0.50, r = 0.45, respectively) and between the expression of oqxAB and rarA (r = 0.462912, r = 0.519354, respectively) in ciprofloxacin resistant isolates. In conclusion, the overexpression of acrAB and oqxAB efflux pumps and the transcriptional regulator marA, soxS and rarA contributed to ciprofloxacin resistance in K. pneumoniae isolates.