Genomic characterization of bla KPC transmission via Tn4401a and Tn4401l transposons across Enterobacteriaceae and ESKAPE in Ecuador

Carbapenem resistance in Enterobacteriaceae poses a major threat to public health because of the limited therapeutic options. The dissemination of the bla KPC gene, which encodes KPC carbapenemases, typically occurs through Tn 4401 transposons and plasmids that facilitate its transmission. In this study, we analysed 802 genomes of ESKAPE pathogens and other Enterobacteriaceae from Ecuador, including both clinical and non-clinical isolates, to determine the prevalence and genetic context of bla KPC-2 and bla KPC-3 and their associated mobile genetic elements. Whole-genome analysis revealed several isolates carrying bla KPC , with bla KPC-3 restricted to Klebsiella pneumoniae . While most isolates harboured the Tn 4401a transposon, we identified a novel variant, Tn 4401l , in two K. pneumoniae isolates collected between 2020 and 2021. Additionally, two putative plasmids carrying Tn 4401a were reconstructed: pECU0072020, a mosaic multidrug-resistant plasmid with a unique genetic organization, and pECU0062021, a more compact structure carrying only bla KPC-2 . The findings demonstrate the wide distribution of bla KPC within diverse bacterial hosts across multiple regions of Ecuador, the emergence of a novel Tn 4401l variant and the presence of putative plasmids that could potentially accelerate multidrug resistance dissemination. This study highlights the need for continuous genomic surveillance and coordinated strategies and practices regarding the use of antibiotics to mitigate the risk of outbreaks and interspecies transmission of carbapenem resistance.