High level of carbapenem resistance and transmission ability of bla_IMP-26 in multidrug-resistant Enterobacter xiangfangensis isolates from China

The emergence of metallo-beta-lactamase gene variants, such as bla_IMP-26, has posed a significant challenge to bacterial infection treatment, drawing considerable attention in public health. This study aims to investigate the resistance mechanism of bla_IMP-26-carrying clinical Enterobacter xiangfangensis in China. bla_IMP-26-harboring carbapenem-resistant Enterobacteriaceae (CRE) isolates were collected from a multicenter study across China. The bla_IMP-26 was identified by polymerase chain reaction (PCR). Multi-locus sequence typing (MLST) and phylogenetic analysis were conducted to investigate the genetic evolutionary characterization of Enterobacteriaceae carrying bla_IMP-26. The genomic contexts of these strains were explored by whole genome sequencing, while conjugation and plasmid stability assays were conducted to assess the transferability and maintenance of the resistance plasmids. Furthermore, the antibiotic susceptibility of IMP-26 to β-lactams was evaluated through antimicrobial susceptibility testing, enzyme kinetic analysis, and molecular docking. Five bla_IMP-26-carrying strains were collected, and all were multidrug-resistant Enterobacter xiangfangensis. bla_IMP-26 was located either on IncHI2/2A or the novel IncpKPC-CAV1321 plasmid, both exhibiting high and stable self-transfer frequency. In addition, bla_IMP-26 was identified within a novel class 1 integron In437, or the classical integron In837. Antimicrobial susceptibility testing and enzyme kinetic assay further showed that IMP-26 could mediate high levels of resistance to common carbapenem and cephalosporin antibiotics. This study characterized the genomic and clinical characteristics of bla_IMP-26-carrying clinical Enterobacter xiangfangensis in China. The high carbapenem resistance and transmission capacity of bla_IMP-26 highlight the need for enhanced surveillance and preventive measures to contain the spread of bla_IMP-26. IMPORTANCE Our research has led to the documentation of a novel IncpKPC-CAV1321 plasmid and the discovery of a novel integron In437, both carrying the bla_IMP-26 gene. A comprehensive analysis of the carbapenem resistance levels and enzymatic kinetics exhibited by IMP-26 revealed that IMP-26 could mediate high levels of resistance to common carbapenem and cephalosporin antibiotics. Our findings underscore the critical need for enhanced surveillance and preventive measures to curtail the dissemination of bla_IMP-26.