Global emergence, evolution and international dissemination of the ST145 Klebsiella oxytoca lineage

Abstract Klebsiella oxytoca is an under-recognised opportunistic pathogen increasingly associated with severe antimicrobial-resistant infections. Here, we report the first carbapenemase-producing K. oxytoca (CPKO) isolate co-harbouring bla KPC-2 and tmexCD2-toprJ2 on a conjugative IncFrepB(R1701) plasmid with interspecies transferability. To place this resistance convergence in context, we analysed 1299 genomes from 42 countries and found that the global burden and diversity of K. oxytoca have been underestimated, with marked geographical heterogeneity in CPKO. Despite broad sequence-type diversity, ST145 emerged as the dominant global lineage, particularly among CPKO, with an expanded resistome and dense insertion sequence content. Bayesian phylogeographical analysis suggested that ST145 may have emerged around 1980, with Poland as the most probable ancestral location in the model, followed by inferred spread across Europe, Asia, and the Americas, with China possibly serving as a secondary hub for onward dissemination. Genome-wide association analysis revealed reinforced metabolic circuits in ST145, suggesting enhanced physiological fitness that may facilitate persistence and dissemination. Together, these findings support enhanced surveillance of CPKO, particularly the emerging ST145 lineage.