Co-occurrence of carbapenem and tigecycline resistance genes in ST1545 Klebsiella pneumoniae clinical isolates from China.

OBJECTIVE

The global rise of pathogens co-resistant to carbapenems and tigecycline represents a critical public health threat. This study aimed to characterize clinical K. pneumoniae co-harbouring carbapenem and tigecycline resistance genes, focusing on their co-occurrence and transmission mechanisms.

METHODS

Clinical K. pneumoniae isolates co-carrying carbapenemase and tigecycline resistance genes were screened by PCR. Isolates were further characterized using antimicrobial susceptibility testing, conjugation experiments, whole-genome sequencing, and bioinformatics analysis. Publicly available genomes of ST1545 K. pneumoniae and K. pneumoniae co-harbouring tmexCD-toprJ and blaNDM/blaKPC were retrieved for comparative analysis.

RESULTS

Seven multidrug-resistant ST1545 K. pneumoniae isolates co-harbouring blaNDM-1 and blaKPC-2 were identified, with three additionally carrying tmexCD2-toprJ2. In seven isolates, blaNDM-1 genes were located on non-conjugative multi-replicon plasmids, three of which co-harboured tmexCD2-toprJ2, while blaKPC-2 resided on conjugative IncFII plasmids. Genetic environment analysis indicated that ISKpn14, ISKpn28, IS26, and class 1 integron facilitate mobilization of blaNDM-1, tmexCD2-toprJ2 and blaKPC-2. Analysis across 13 ST1545 K. pneumoniae isolates revealed SNP changes associated with plasmid and resistance genes acquisition. Analysis of 84 K. pneumoniae strains co-harbouring tmexCD-toprJ and blaNDM/blaKPC showed diverse STs, a primary human origin in China, and a high burden of resistance genes, with blaNDM-1, blaKPC-2, and tmexCD1-toprJ1/tmexCD2-toprJ2 as predominant variants.

CONCLUSIONS

This study first reported the convergence of blaNDM-1, blaKPC-2, and tmexCD2-toprJ2 in ST1545 K. pneumoniae, highlighting the pivotal role of diverse mobile genetic elements in the accumulation and dissemination of carbapenem and tigecycline resistance. ST1545 K. pneumoniae may represent a potential reservoir for these critical resistance determinants, warranting continuous surveillance.