Coexistence of blaKPC-2 and blaNDM-1 in one IncHI5 plasmid confers transferable carbapenem resistance from a clinical isolate of Klebsiella michiganensis in China

Objectives: This study firstly identified an IncHI5 plasmid pK254-KPC_NDM co-carrying two different class carbapenemase genes blaKPC-2 and blaNDM-1 in Klebsiella michiganensis K254.Methods: The strain K254 was sequenced by high-throughput genome sequencing. A detailed genomic and phenotypic characterization of pK254-KPC_NDM was performed.Results: pK254-KPC_NDM displayed the conserve IncHI5 backbone and carried a resistant accessory region: Tn 1696 -related transposon Tn 7414 containing blaKPC-2 and blaNDM-1 . A sequence comparison was applied to a collection of four Tn 1696 -related transposons (Tn 7414 -Tn 7417 ) harbouring carbapenemase genes. For all these four transposons, the bla NDM-1 was carried by Tn 125 derivatives within three different mobile genetic elements. Tn 7414 further acquired another carbapenemase gene, blaKPC-2 , because of the integration of the local blaKPC-2 genetic environment from Tn 6296 , resulting in the high-level carbapenem resistance of K. michiganensis K254. The conjugal transfer and plasmid stability experiments confirmed that pK254-KPC_NDM could be transferred intercellularly and keep the stable vertical inheritance in different bacteria, which would contribute to the further dissemination of multiple carbapenemase genes and enhance the adaption and survival of K. michiganensis under complex and diverse antimicrobial selection pressures.Conclusion: This study was the first to report the K. michiganensis isolate coharbouring blaKPC-2 and blaNDM-1 in the Tn 1696 -related transposon in IncHI5 plasmid. The emergence of novel transposons simultaneously carrying multiple carbapenemase genes might contribute to the further dissemination of high-level carbapenem resistance in the isolates of the hospital settings and pose new challenges for the treatment of nosocomial infection. (c) 2023 The Author(s).Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )