Dissemination of OXA-23 carbapenemase-producing Proteus mirabilis and Escherichia coli is driven by transposon-carrying lineages in the UK.

Carbapenem-resistant Enterobacterales are a significant threat to global public health. Here, we characterize bla OXA-23-positive Proteus mirabilis (n=8) and Escherichia coli (n=3) isolates from human clinical samples collected between 2021 and 2024 in the UK. Whole-genome sequencing (WGS) was used to generate data, and a phylogenetic tree inferred from SNPs filtered for recombination was constructed to assess the genomic relatedness among the isolates. To provide an international context, we included publicly available genomes. Short-read mapping to a reference genome enabled reconstruction of the genomic neighbourhood around bla OXA-23. Minimum inhibitory concentration (MIC) determination was performed using broth microdilution and results interpreted using the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. UK P. mirabilis isolates belonged to ST142 and formed a sub-clade descending from an ancestral cluster of French isolates with relatively few SNPs between them (9-39). E. coli ST38 isolates harboured bla OXA-23 and showed close genetic relatedness (12-15 SNPs) among themselves. In P. mirabilis, bla OXA-23 was associated with transposon Tn6703, while E. coli harboured a novel composite transposon, designated Tn7816, bordered by two copies of IS26 and with three copies of bla OXA-23. bla OXA-23 was integrated into the chromosome in all isolates. All isolates were resistant to amoxicillin/clavulanic acid (>32 mg l-1) and with meropenem MICs above the EUCAST screening cut-off (0.5-1 mg l-1). In conclusion, UK bla OXA-23-positive P. mirabilis isolates belong to the same clonal lineage (ST142) previously reported in Belgium, Germany, Switzerland and France, suggesting introduction of this lineage into the UK. This is the first report of an E. coli ST38 lineage with chromosomally encoded bla OXA-23 located within a novel transposon Tn7816. WGS plays an important role in identifying the mechanism(s) of transmission of emerging carbapenemase genes.