Phenotypic and genotypic characterization of clinical carbapenem-resistant Acinetobacter species harboring the metallo-beta-lactamases IMP-8 or NDM-1 in China

Carbapenem-resistant Acinetobacter spp. pose a significant challenge in clinical settings due to limited treatment options for nosocomial infections. Carbapenem-hydrolyzing class D beta-lactamases are the primary cause for carbapenem resistance, while metallo-beta-lactamases (MBLs) New Delhi metallo beta-lactamase (NDM) and imipenemase (IMP) also contribute. This study investigated five MBL-producing Acinetobacter spp. strains isolated from a clinic in China in 2010. The bla_IMP-8-carrying A1014 was the first identified CRAB among all known ST_Pas150 isolates worldwide. Through whole-genome sequencing and the southern blot analysis, we determined that bla_IMP-8 was located on a pR4WN-type plasmid and bla_NDM-1 was located on four distinct pSU1904NDM-type plasmids. The bla_IMP-8 gene was identified within a class 1 integron organized as a 5'-conserved segment (intI), variable region (bla_IMP-8-aac(6')-Ib), and 3'-conserved segment (qacEΔ1/sul1). All available sequences of bla_IMP variants in A. baumannii from the NCBI were investigated and classified into five types of class 1 integrons. All bla_NDM-1 plasmids were transferable, and the bla_NDM-1 genes were in a conservative region. Additionally, multiple resistance genes, including those conferring resistance to aminoglycosides, tetracyclines, and macrolides, were detected on plasmids from these strains. All strains were resistant to meropenem and imipenem, while they were all susceptible to tigecycline and intermediate to polymyxin. A207 and A1014 were susceptible to cefiderocol, and only bla_IMP-8-carrying A1014 had low MIC value (4/2 µg/mL) toward cefoperazone/sulbactam. In conclusion, we characterized the phenotypic and genotypic features of one IMP-8-producing and four NDM-1-producing plasmids recovered from Acinetobacter spp. strains isolated in 2010, contributing to the understanding of the dissemination and evolution of these enzymes.

Importance: Given the low prevalence of IMP among A. baumannii and the limited sequencing technology in earlier years, research on bla_IMP in A. baumannii is scarce, and genetic information on bla_NDM-1-producing Acinetobacter spp. strains isolated in earlier years is limited. This study revisited five MBL-carrying Acinetobacter spp. strains isolated in 2010, characterizing their phenotypic and genotypic features. This retrospective analysis serves as a form of "bacterial archaeology," providing evidence of the evolutionary changes in genetic elements conferring antibiotic resistance.