High Expression of Metallo-[beta]-Lactamase Contributed to the Resistance to Carbapenem in Clinical Isolates of Pseudomonas aeruginosa from Baotou, China

Background: Bacterial resistance to antibiotics has become a major public health concern. This study aimed to determine the resistance mechanisms to carbapenem in clinical isolates of Pseudomonas aeruginosa. Methods: A total of 62 clinical isolates of carbapenem-resistant P. aeruginosa (CRPA) were collected from 2015 to 2017. Imipenem (IPM)-EDTA disk synergy test was used to screen strains that produced metallo-[beta]-lactamase. In addition, the genes for outer membrane protein OprD2, metallo-P-lactamase and mexR gene were amplified and sequenced. Expression of mexA was detected by real-time PCR. Results: Disk synergy test showed that 51.6% (32/62) of the strains were positive for metallo-[beta]-lactamase. PCR showed that 84.4% of the strains were SIM-positive (27/32), 15.6% of the strains were IMP-positive (5/32), and 12.5% of the strains were VIM-positive (4/32). SPM-positive and GIM-positive strains were not detected. In addition, 5 of the 62 strains had small deletions and/or point mutations in OprD2. Three strains had a high expression of mexA, while eight strains were positive for the regulatory gene mexR with no mutations detected by DNA sequencing. Conclusion: Expression of metallo-[beta]-lactamase is the main resistance mechanism of P. aeruginosa to carbapenem. Mutations in OprD2 and/or the overexpression of efflux pump MexAB-OprM may contribute to P. aeruginosa resistance to carbapenem. Keywords: Pseudomonas aeruginosa, carbapenem, metallo-[beta]-lactamase, outer membrane protein OprD2, efflux pump MexAB-OprM