Comprehensive genomic analysis of clinical Serratia marcescens isolates unveils extensive dissemination and genetic context of co-occurring of blaKPC-2 and blaCTX-M-14 resistance genes

Serratia marcescens has emerged as an important multidrug-resistant pathogen implicated in hospital-acquired infections. However, detailed genomic insights into the genetic contexts and dissemination mechanisms of carbapenemase and extended-spectrum β-lactamase (ESBL) genes in this species remain limited. This study aimed to elucidate the genomic features and evolutionary relationships among clinical S. marcescens isolates harboring carbapenem and ESBL resistance determinants. We conducted whole-genome sequencing and comparative genomic analyses of 11 clinical multidrug-resistant S. marcescens isolates from a tertiary hospital in eastern China. Two isolates (YQ11402 and YQ114022) concurrently harbored the carbapenemase gene blaKPC-2 and the ESBL gene blaCTX-M-14, predominantly located within IS26-associated composite mobile genetic elements on conserved IncR and IncFII-type plasmids. These isolates exhibited extensive co-resistance to aminoglycosides, fluoroquinolones, and tetracyclines mediated by additional plasmid-borne genes such as aac(6′)-Ic, oqxAB, qnrS1, and tet(41). Comparative analysis revealed significant genetic similarity (> 99% nucleotide identity) between resistance plasmids identified in S. marcescens and those previously reported in Klebsiella pneumoniae and Escherichia coli, underscoring interspecies dissemination. Phylogenomic analysis using average nucleotide identity (ANI) indicated clonal relationships among the majority of isolates, highlighting potential intra-hospital transmission events. Our findings reveal that clinical isolates of S. marcescens act as reservoirs for high-risk resistance genes, notably blaKPC-2 and blaCTX-M-14, located on highly conserved and transmissible plasmid backbones. These results underscore the critical need for genomic surveillance to monitor this pathogen's role in resistance dissemination, thereby informing more effective infection prevention and antimicrobial stewardship practices.