Overexpression of Efflux Pumps AcrAB and OqxAB Contributes to Ciprofloxacin Resistance in Clinical Isolates of K. pneumonia

Background: Infection caused by multidrug-resistant K. pneumoniae is regarded as a severe public health concern worldwide, with most countries reporting an increase in fatality rates over time. Efflux pumps are significant determinants of acquired and/or intrinsic resistance in K. pneumoniae. Objectives: Our aim is to explore efflux-mediated resistance mechanisms in K. pneumoniae by using quantitative real-time PCR in order to evaluate the expression of efflux pump genes (acrA, acrB, oqxA, and oqxB) and pump regulators (marA, soxS, and rarA). Methods: Efflux pump inhibitor CCCP reduced MIC values of ciprofloxacin by 2 to 64-fold in 43/46 (93%) of MDR-K. pneumoniae isolates. Results: Compared to the control strain (untreated one), our results demonstrated that acrA, acrB, oqxA, oqxB, marA, soxS, and rarA were overexpressed in 29 (63%), 24 (52%), 29 (63%), 24 (52%), 17 (37%), 16 (35%), and 16 (35%) of K. pneumoniae isolates, respectively. Additionally, a positive correlation was established between the expressions of acrAB and marA (r = 0.50, r = 0.45, respectively) and oqxAB and rarA (r = 0.462912, r = 0.519354, respectively). Conclusion: Ciprofloxacin resistance was caused by overexpression of the efflux pump genes acrAB and oqxAB, as well as the transcriptional regulators marA, soxS, and rarA in clinical isolates of K. pneumonia.