Dissemination of OXA-23 carbapenemase-producing Proteus mirabilis and Escherichia coli is driven by transposon-carrying lineages in the UK
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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 2021–2024 in the UK. Whole genome sequencing (WGS) was used to generate data, and a core gene SNP-based phylogenetic tree 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 neighborhood around bla OXA-23 . Minimum inhibitory concentration (MIC) determination was performed using broth microdilution and results interpreted using EUCAST guidelines. UK P. mirabilis isolates belonged to ST142 and were closely related (2–13 SNPs) to French isolates from 2017-2019. E. coli ST38 isolates harboured bla OXA-23 and showed high genetic relatedness (5–9 SNPs) among themselves. In P. mirabilis , bla OXA-23 was associated with transposon Tn 6703 , while E. coli harboured a novel composite transposon, designated Tn 7816 , bordered by two copies of IS 15DIV 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) and with meropenem MICs above the EUCAST screening cut-off (0.5–1 mg/L). 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 Tn 7816 .
WGS plays an important role in identifying the mechanism(s) of transmission of emerging carbapenemase genes.
IMPACT STATEMENT
Most diagnostic assays primarily focus on detection of the ‘big 5’ carbapenemase gene families (KPC, OXA-48-like, NDM, VIM and IMP), which are globally dominant in Enterobacterales. OXA-23-like carbapenemase genes are predominantly identified in Acinetobacter baumannii meaning that their presence in Enterobacterales is likely underestimated. In this study, we report the identification of bla OXA-23 in Proteus mirabilis and Escherichia coli isolated from UK clinical samples following incorporation of bla OXA-23-like as a target in the multiplex-PCR assay used to screen all Gram-negative bacteria referred to the UK’s national reference laboratory for investigation of carbapenem resistance. To enhance our understanding of the genomic epidemiology of bla OXA-23 we utilized short-read sequencing to characterize all isolates, and long-read assembly polished with short-read to determine the genomic context of bla OXA-23 in E. coli . WGS analysis provided invaluable insights into the genomic relatedness among the isolates, identifying that bla OXA-23 -positive P. mirabilis isolates were closely related to those previously reported in Europe and uncovered a novel transposon associated with bla OXA-23 in E. coli . In addition, bla OXA-23 was chromosomally located in all isolates, with the potential for stable vertical inheritance. The results of this study highlight the need to further characterize Enterobacterales isolates suspected of carbapenemase production but negative for the ‘big 5’ carbapenemase gene families and further demonstrates the role of WGS in characterizing bacterial strains and mobile genetic elements associated with the emergence and transmission of antimicrobial resistance mechanisms.
DATA SUMMARY
Illumina short-read, contigs and MIC (if available) data for P. mirabilis (n=8) and E. coli (n=3) bla OXA-23 -positive isolates from the UK are available in the ENA database under Bioproject PRJEB80458. The Illumina polished version of the long-read-only (Nanopore) assembly for 1697008 (ES1) E. coli isolate is accessible under the assembly accession number GCA_964341145. The accession number for each genome and the metadata generated in this study are provided in the Table 1.
