Synergistic effect of copper oxide nanoparticles and chloramphenicol antibiotic on MexA gene expression of pump efflux system in drug-resistant Pseudomonas aeruginosa isolates

Abstract

Background. Pseudomonas aeruginosa is a causative agent of nosocomial infections. Chloramphenicol is a broad-spectrum, inexpensive, and common antibiotic. MexAB-OprM is a secretory pump that causes the innate resistance of this bacterium. This study aimed to evaluate the expression of MexA gene under the treatment of copper nanoparticles and chloramphenicol. Methods. In this study, 49 samples were collected from 11 laboratories in Mashhad, Iran.Abundance of Me gene MexA was done by polymerase chain reaction (PCR) method, and antibiotic susceptibility assessment was performed by disk diffusion method. To calculate minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC), copper nanoparticles, and a combination of both, the broth dilution method was performed. Microdilution method and real time PCR technique were used to determine the effective dilution of copper oxide nanoparticles and chloramphenicol antibiotics and expression of MexA gene, respectively. Result. The identity of 49 strains was confirmed. All strains had the MexA gene and were resistant to more than two antibiotics. The MIC of bacterial strains was 250 μg/ml for copper oxide nanoparticles and 62.50 μg/ml for chloramphenicol antibiotic. Compared to antibiotics, copper nanoparticles had a greater effect on MIC, though it was lower than the combined effect of antibiotics and copper oxide nanoparticles. Conclusion. Copper oxide nanoparticles or the synergistic effect of copper oxide nanoparticles and chloramphenicol antibiotics are effective in reducing MexA gene expression. Practical Implications. Nanoparticles are an important option for use as an alternative to or supplement to antibiotics. Also, copper oxide nanoparticles are more effective to inhibit bacterial growth when used in combination with antibiotics.