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Genomic diversity of EPEC associated with clinical presentations of differing severity

Abstract

Enteropathogenic Escherichia coli (EPEC) are diarrhoeagenic E. coli, and are a significant cause of gastrointestinal illness among young children in developing countries. Typical EPEC are identified by the presence of the bundle-forming pilus encoded by a virulence plasmid, which has been linked to an increased severity of illness, while atypical EPEC lack this feature. Comparative genomics of 70 total EPEC from lethal (LI), non-lethal symptomatic (NSI) or asymptomatic (AI) cases of diarrhoeal illness in children enrolled in the Global Enteric Multicenter Study was used to investigate the genomic differences in EPEC isolates obtained from individuals with various clinical outcomes. A comparison of the genomes of isolates from different clinical outcomes identified genes that were significantly more prevalent in EPEC isolates of symptomatic and lethal outcomes than in EPEC isolates of asymptomatic outcomes. These EPEC isolates exhibited previously unappreciated phylogenomic diversity and combinations of virulence factors. These comparative results highlight the diversity of the pathogen, as well as the complexity of the EPEC virulence factor repertoire.

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Figure 1: Phylogenomic analysis of the 70 EPEC isolates associated with clinical outcomes of differing severity compared with select previously sequenced AEEC genomes and a reference collection of 25 diverse E. coli and Shigella isolate genomes.
Figure 2: Identification of genes associated with symptomatic and asymptomatic EPEC isolates.

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Acknowledgements

This project was funded by federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services NIH grant no. U19 AI090873.

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Contributions

T.H.H., M.S.D., J.P.N. and D.A.R. conceived and designed the experiments. T.H.H., M.S.D., E.M.B., J.B.K., J.P.N. and D.A.R. performed the experiments. T.H.H., M.S.D., E.M.B., J.B.K., J.P.N. and D.A.R. analysed the data. S.P., M.A., A.H., I.M., J.B.O., T.R., B.T., S.Q., F.Q., A.Z., K.L.K., M.M.L. and J.P.N. contributed materials from the GEMS studies. T.H.H., M.S.D., E.M.B., J.B.K., J.P.N. and D.A.R. co-wrote the paper.

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Correspondence to Michael S. Donnenberg or David A. Rasko.

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The authors declare no competing financial interests.

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Supplementary Results, Figures 1–6, References and Tables 1–10 (PDF 8881 kb)

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Hazen, T., Donnenberg, M., Panchalingam, S. et al. Genomic diversity of EPEC associated with clinical presentations of differing severity. Nat Microbiol 1, 15014 (2016). https://doi.org/10.1038/nmicrobiol.2015.14

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