Plasmidome analyses of Klebsiella pneumoniae co-producing blaKPC-2 and blaNDM-1 in Southern Brazil : characterisation of mobile genetic elements

Abstract

Objective: Infections due to carbapenemase-producing Enterobacterales harbouring more than one carbapenemase-encoding gene spread mainly by plasmid and transposon mobilisation. The objective of this study was to analyse the mobile genetic elements carrying blaKPC and blaNDM of Klebsiella pneumoniae carbapenemase co-producers (KpKN). Methods: K. pneumoniae isolates with reduced susceptibility to carbapenems were obtained between 2016 and 2023. To evaluate the genetic environment of KpKN, 22 isolates were selected for antimicrobial susceptibility testing and whole-genome sequencing. Results: The blaKPC-2 gene was carried mainly by IncN/IncFIB, a novel co-integrated plasmid in the Tn 4401b transposon. blaNDM-1 was disseminated in the only two KpKN isolates recovered prior to 2020 by the IncHI1B/IncFIB plasmid type within the Tn 30 0 0 transposon. Significantly, isolates obtained since 2020 showed the blaNDM-1 gene carried by IncA/C in an IS 26 -flanked pseudo-composite transposon contain- ing IS CR1 , which also had genes that conferred resistance to sulfonamides, aminoglycosides, macrolides, quinolones, amphenicols, tetracyclines, rifampicin, sulfonamide, and trimethoprim. The isolates belonged mainly to ST11 and ST16. Conclusions: Plasmid and transposon changes during different periods could be related to higher dissem- ination of blaNDM-1 , and the large number of resistance genes present in the IS 26 -flanked transposon may have increased co-selection of this plasmid through the wide use of antimicrobials during the pandemic.