Functional analysis of colonization factor antigen I positive enterotoxigenic Escherichia coli identifies genes implicated in survival in water and host colonization

Author:

Abd El Ghany Moataz1234ORCID,Barquist Lars56ORCID,Clare Simon7,Brandt Cordelia7,Mayho Matthew7,Joffre´ Enrique8ORCID,Sjöling Åsa8ORCID,Turner A. Keith97ORCID,Klena John D.10ORCID,Kingsley Robert A.97,Hill-Cawthorne Grant A.11ORCID,Dougan Gordon127,Pickard Derek127

Affiliation:

1. Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, Sydney, Australia

2. The Westmead Institute for Medical Research, University of Sydney, Sydney, Australia

3. King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia

4. The Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, Australia

5. Faculty of Medicine, University of Würzburg, Würzburg, Germany

6. Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI), Würzburg, Germany

7. The Wellcome Trust Sanger Institute (WTSI), the Wellcome Trust Genome Campus, Hinxton, Cambridge, UK

8. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden

9. Quadram Institute Bioscience, Norwich Research Park, Norwich, UK

10. Centers for Disease Control and Prevention, Atlanta, Georgia, USA

11. School of Public Health, the University of Sydney, Sydney, Australia

12. Department of Medicine, University of Cambridge, Cambridge, UK

Abstract

Enterotoxigenic Escherichia coli (ETEC) expressing the colonization pili CFA/I are common causes of diarrhoeal infections in humans. Here, we use a combination of transposon mutagenesis and transcriptomic analysis to identify genes and pathways that contribute to ETEC persistence in water environments and colonization of a mammalian host. ETEC persisting in water exhibit a distinct RNA expression profile from those growing in richer media. Multiple pathways were identified that contribute to water survival, including lipopolysaccharide biosynthesis and stress response regulons. The analysis also indicated that ETEC growing in vivo in mice encounter a bottleneck driving down the diversity of colonizing ETEC populations.

Funder

Wellcome Trust

Marie Bashir Institute and Sydney Medical School Foundation

NIMR Cambridge BRC Antibiotic Resistance theme

The Swedish Research Council

BBSRC Institute Strategic Programme Microbes in the Food Chain

Publisher

Microbiology Society

Subject

General Medicine

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