Molecular epidemiology of extended-spectrum beta-lactamaseproducing Klebsiella pneumoniae bloodstream infections from Aberdeen, Scotland, and their comparison to isolates from England

Klebsiella spp., the second leading cause of bacteraemia in the UK, are major nosocomial pathogens. We investigated the epidemiology of extended-spectrum β-lactamase (ESBL)-producing Klebsiella spp. in Aberdeen, Scotland and England. Twenty-four ESBL producers underwent whole-genome sequencing and typing using MLST. Sequence types were queried in the Bacterial Isolate Genome Sequence Database (BIGSdb) to assess phylogenetic relationships using Parsnp, and resistance/virulence genes were identified by Kleborate. Plasmids were assembled with plasmidSPAdes. All isolates had the bla_SHV, with three positive for bla_SHV-12 ESBL and two positive for bla_DHA-1 ESBL. The bla_CTX-M was observed in 71% (33% plasmid-borne), bla_TEM in 42%, with all isolates resistant to ceftazidime, cefotaxime and cefuroxime. Two isolates carried mcr-9.1 on 2.5 and 203 kb plasmids. MLST identified 21 strains, with ST-13 and ST-200 being the most common. BIGSdb revealed 487 similar strains across 43 clonal groups. ST14 (34%) and ST15 (29%) were predominant multidrug-resistant strains. Nearly all isolates (99%) harboured the bla_SHV (43% SHV-28, 2% SHV-12 ESBL), and 57% carried a bla_CTX-M . Carbapenemases were detected in 61% of isolates, and 59% had gyrA/parC mutations, exclusively linked to strains from England. ST432 strains from humans (resistant) and cattle (sensitive) were closely related. We also observed ST14 and ST15 (CC15) as high-risk clones thought to have evolved independently that are globally prevalent. The coexistence of mcr-9.1 and plasmid ESBL bla_CTX-M in Klebsiella spp. threatens the efficacy of critically important antibiotics. The close relatedness of human and cattle ST432 strains suggests potential zoonotic transmission, emphasizing the role of livestock as a reservoir for antimicrobial-resistant pathogens and the need for genomic epidemiology studies to elucidate transmission pathways and interspecies exchange. A One Health approach integrating human, animal and environmental surveillance would enhance our understanding of the molecular dynamics and evolutionary trajectory of Klebsiella pneumoniae, reinforcing the need for targeted interventions to limit the spread of antimicrobial resistance.