Copper induced augmentation of antibiotic resistance in Acinetobacter baumannii MCC 3114

Increasing antibiotic resistance among the common nosocomial pathogen i.e. Acinetobacter baumannii poses life threat to the health care workers as well as to the society. The dissemination of antibiotic resistance in this pathogen at an alarming rate could be not only due to the overuse of antibiotics but also due to the stress caused by exposure of bacterium to several environmental contaminants in their niches. In the present study, effect of copper stress on augmentation in the antibiotic resistance of A. baumannii MCC 3114 against three clinically used antibiotics was investigated along with the phenotypic and genotypic alterations in the cell. It induced 8, 44 and 22-fold increase in resistance against colistin, ciprofloxacin and levofloxacin, respectively. Moreover, the biofilm formation of adapted culture was significantly enhanced due to a dense EPS around the cell (as revealed by SEM images). The structural changes in EPS were demonstrated by FTIR spectroscopy. The adequate growth of adapted MCC 3114 despite increased level of ROS indicates its persistence in copper and ROS stress. The physiological alterations in cell viz., increased efflux pump activity and decreased membrane permeability was observed. Molecular analysis revealed increased expression of efflux pump related genes, oxidative stress genes, integron and antibiotic resistance genes. In sum, our study revealed that the exposure of the critical pathogen, A. baunmannii to copper in hospital settings and environmental reservoirs can impose adaptive pressure which may lead to genotypic as well phenotypic changes in cell resulting into the augmentation of antibiotic resistance.