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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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.

Author information

Affiliations

  1. University of Maryland School of Medicine, Institute for Genome Sciences, 801 W. Baltimore Street, Room 600, Baltimore, Maryland 21201, USA

    • Tracy H. Hazen
    •  & David A. Rasko
  2. Department of Microbiology and Immunology, University of Maryland School of Medicine, 685 West Baltimore Street, HSF-I Suite 380, Baltimore, Maryland 21201, USA

    • Tracy H. Hazen
    • , Eileen M. Barry
    • , James B. Kaper
    •  & David A. Rasko
  3. Department of Medicine, University of Maryland School of Medicine, University of Maryland Medical Center, N3W42, 22 S. Greene Street, Baltimore, Maryland 21201, USA

    • Michael S. Donnenberg
    •  & Eileen M. Barry
  4. Center for Vaccine Development, University of Maryland School of Medicine, 685 West Baltimore Street, Room 480, Baltimore, Maryland 21201, USA

    • Sandra Panchalingam
    • , Karen L. Kotloff
    •  & Myron M. Levine
  5. Medical Research Council Unit, Atlantic Boulevard, Fajara, P.O. Box 273, Banjul, Gambia

    • Martin Antonio
  6. ICDDR, B, GPO Box 128, Dhaka 1000, Bangladesh

    • Anowar Hossain
  7. Centro de Investigacao em Saude, Manhica, Rua 12, Cambeve, Vila de Manhiça, CP 1929, Maputo, Mozambique

    • Inacio Mandomando
  8. Kenya Medical Research Institute/CDC, P.O. Box 54840 – 00200, Kisumu, Kenya

    • John Benjamin Ochieng
  9. National Institute of Cholera and Enteric Diseases, P-33, C.I.T. Road, Scheme XM, Beleghata, Kolkata 700 010, India

    • Thandavarayan Ramamurthy
  10. Center for Vaccine Development – Mali, Bamako, Mali

    • Boubou Tamboura
  11. The Aga Khan University, Stadium Road, P.O. Box 3500, Karachi 74800, Pakistan

    • Shahida Qureshi
    • , Farheen Quadri
    •  & Anita Zaidi
  12. Department of Pediatrics, University of Virginia School of Medicine, P.O. Box 800386, Charlottesville, Virginia 22908, USA

    • James P. Nataro

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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.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

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

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DOI

https://doi.org/10.1038/nmicrobiol.2015.14

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