Antimicrobial Resistance Mechanisms in Carbapenem-Resistant <i>Pseudomonas aeruginosa</i> Clinical Strains Isolated in Shanghai, China

Carbapenems, as the preferred treatment for multidrug-resistant <i>Pseudomonas aeruginosa</i>, are increasingly facing issues of insufficient therapeutic efficacy. This study aims to investigate the antimicrobial resistance mechanisms of clinical <i>P. aeruginosa</i> isolates to carbapenems. The whole genome sequencing revealed various β-lactamase genes, including the intrinsic genes <i>bla</i> _PAO and <i>bla</i> _OXA-50-like, as well as the acquired <i>bla</i> _GES-5 (n = 6), and <i>bla</i> _OXA-101 (n = 10) in 40 carbapenem-resistant <i>P. aeruginosa</i> (CRPA) isolates. These isolates were categorized into 18 different sequence types, with ST235 (n = 6) and ST270 (n = 10) being the most prevalent. Single nucleotide polymorphism (SNP) analysis revealed that the collected isolates can be divided into two evolutionary branches, with some exhibiting high homogeneity. Isolates belonging to ST207, ST235, ST270, and ST277 may have contributed to small-scale outbreaks of infection in the hospital. A total of 5 different class 1 integrons, including a new gene cassette array <i>bla</i> _GES-5 -<i>gcuE15-aph(3')-XV-ISPa21e</i>, were detected in this study. All 40 CRPAs were found to have mutations in the outer membrane porin OprD. The efflux pump gene <i>mexY</i> showed the highest overexpression frequency at 55.00% (22/40). The CRPAs that overexpress <i>mexY</i> showed a higher resistance rate to various antimicrobial agents than those with normal levels of <i>mexY</i> expression (<i>p</i> < 0.05). Of 40 CRPAs, four isolates carried four antimicrobial resistance mechanisms simultaneously (<i>bla</i> _GES-5, OprD mutation, high expression of efflux pump, and biofilm formation). To the best of our knowledge, a new gene cassette array of class 1 integron, <i>bla</i> _GES-5-<i>gcuE15</i>-<i>aph(3'</i>)-<i>XV</i>-<i>lSPa21e</i>, was reported for the first time in this study.