Abstract
Background
Escherichia coli clonal complex 38 (CC38) is a genetically diverse lineage increasingly linked to antimicrobial resistance and extraintestinal infections in humans. Despite its clinical and epidemiological relevance, its population structure, zoonotic potential, and ecological associations remain poorly understood.
Methods
We analyzed 242 human E. coli CC38 bloodstream isolates collected through Danish national surveillance, 83 isolates from food and production animals, and 2313 international genomes to investigate host associations and transmission dynamics. Phylogenetic reconstruction, Bayesian host prediction based on mobile genetic elements, and statistical testing of plasmid–host associations were used to delineate population structure and identify potential host-associated markers.
Results
Here we show that Danish CC38 isolates belong to multiple sub-lineages, with no evidence of foodborne outbreaks and limited hospital transmission. Bayesian host prediction supports a poultry origin for several distinct human sub-lineages. Global analyses of 2638 genomes reveal two major clusters: a poultry-associated Cluster I and a predominantly human-associated Cluster II, which subdivides into eight sub-lineages with distinct host, resistance, and virulence profiles. Two small plasmids, ColRNAI and Col(MG828), are strongly enriched in poultry and livestock isolates but largely absent from human-associated sub-clusters, indicating their value as host-associated genetic markers.
Conclusions
Our findings refine the phylogenetic structure of E. coli CC38 and identify plasmid markers that may enhance genomic surveillance of zoonotic transmission. These results highlight the importance of a One Health approach to monitor antimicrobial resistance across human, food, and animal reservoirs. Together, these insights support data-driven One Health surveillance and intervention strategies.
Plain language summary
Antibiotic-resistant bacteria are a growing concern for both human and animal health. This study examined a specific group of E. coli bacteria, which can cause serious infections. By comparing the genomes of bacteria, isolated from people, food, and animals in Denmark and around the world, the researchers mapped how different lineages are related and where they are most likely to come from. The results show that some strains found in humans may have originated in poultry. The study also identified two small DNA elements strongly linked to bacteria from poultry and livestock. These elements could help trace how resistant bacteria move between animals and humans, supporting more effective disease surveillance and antibiotic resistance prevention.
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Data availability
All E. coli CC38 sequence data generated as part of the Danish National Surveillance that have not previously been published are deposited in the European Nucleotide Archive (ENA) as part of the BioProjects National Surveillance of ESBL-producing Escherichia coli (BioProject PRJEB75816) and National Surveillance of Carbapenemase-Producing Organisms (BioProject PRJEB75178). Accession numbers for the raw sequencing read data included in this study are provided in Supplementary Data 1. In addition, global Escherichia coli CC38 genome sequences analyzed in this study were obtained from public repositories, including the ENA Sequence Read Archive (SRA), NCBI SRA, and EnteroBase. Accession numbers and assembly barcodes for all publicly available genomes are listed in Supplementary Data 1. The EnteroBase E. coli collection is accessible at https://enterobase.warwick.ac.uk/species/index/ecoli. The source data for Fig. 1 are provided in Supplementary Data 5, and the corresponding phylogenetic tree is proved in Supplementary Data 6. The source data for Fig. 2 are provided in Supplementary Data 7. The phylogenetic tree for Fig. 3 is provided in Supplementary Data 8, and source file for Fig. 3 and Table 1 are provided in Supplementary Data 1 and 4.
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Acknowledgements
Pia Thurø Hansen, Line Toft Madsen and Søren Iversen at Statens Serum Institut are thanked for their excellent laboratory assistance. We also thank Jette Sejer Kjeldgaard, Pimlapas Shinny Leekitcharoenphon, and Natasia Rebekka Thornval at the National Food Institute, Technical University of Denmark, for assistance with sequencing data. Part of this work was supported by the Danish Ministry of Health.
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L.R. and M.S. contributed conceptualization, data curation, formal analysis, investigation, methodology, project administration, software, validation, visualization, writing—original draft, and writing—review and editing. A.M.H. and H.H. contributed conceptualization, original draft, and writing—review and editing. A.R., L.E.B.C., R.S., D.E.P., and M.A. contributed bioinformatic analyses, figure preparation, and writing—review and editing. F.H. contributed laboratory analyses, sequencing, and registration of Danish surveillance isolates, as well as writing—review and editing. F.S. contributed virulence profiling and writing—review, and editing. S.A. and L.B.P. contributed resources, supervision, and writing—review and editing, with additional input on conceptualization and interpretation. R.S.H., B.D.J., J.R.J., B.J.H., L.S., K.S., D.B.H., U.S.J., C.Ø., T.S.S., M.T.K.N., M.W., and H.L.N. contributed resources (isolate collection), data curation, and writing—review and editing.
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Communications Medicine thanks Reuben Maghembe and Ivan Sserwadda for their contribution to the peer review of this work. A peer review file is available.
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Roer, L., Rasmussen, A., Hansen, F. et al. Genomic characterization and sub-clustering of Escherichia coli clonal complex 38 reveal host associated genetic markers. Commun Med (2026). https://doi.org/10.1038/s43856-026-01402-2
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DOI: https://doi.org/10.1038/s43856-026-01402-2
