The Effects Of Azithromycin On MexAB-OprM Efflux Pump And The Antibiotic Resistance In Pseudomonas Aeruginosa

Objective investigate the influence of azithromycin on MexAB-OprM efflux pump in Pseudomonas aeruginosa, in order to provide experimental evidences for reasonable choice of antibiotics in clinical work.Methods The minimal inhibitory concentration (MIC) of Pseudomonas aeruginosa to antibiotics were determined by broth microdilution after treated by efflux pump inhibitor (phenylalanine-arginine-β-naphthalene amide, PAβN). The active efflux positive phenotype strains were chosen according to MIC. Three genes of efflux pumps, mexB, oprM and mexR, were detected by PCR. Then, real-time PCR was used to detect the mRNA level of mexB in positive phenotype strains, while DNA sequencing was performed for mexR in the positive phenotype strains. After treated by azithromycin, the mRNA level of mexB and the MIC of antibiotics such as ciprofloxacin, levofloxacin, ceftazidime and meropenem were also tested in Pseudomonas aeruginosa.Results 8 positive phenotype strains were chosen from 20 clinical multidrugs resistant strains of Pseudomonas aeruginosa. The oprM, mexB and mexR expression were confirmed in all 8 strains, whose expression of mexB mRNA was also significantly higher than that of PAO1. However, mexR mutations was found only in one strain, PAO03. Azithromycin significantly reduced the mexB expression and MICs of ciprofloxacin, levofloxacin, ceftazidime and meropenem in strains which overexpressed the MexAB-oprM but have no mexR mutation. However, the mexB expression and MICs in PAO03 and nalB strain were not influenced by azithromycin. Conclusion Azithromycin can suppress the gene expression of MexAB-OprM efflux pump, thus elevates the susceptation of pseudomonas aeruginosa to antibiotics.