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Escherichia Coli Killing by Epidemiologically Successful Sublineages of Shigella Sonnei is Mediated by Colicins

28 Pages Posted: 10 Jan 2023

See all articles by P. Malaka De Silva

P. Malaka De Silva

University of Liverpool - Department of Clinical Infection, Microbiology and Immunology

Rebecca J. Bennett

University of Liverpool - Department of Clinical Infection, Microbiology and Immunology

Lauriane Kuhn

CNRS - Plateforme Proteomique Strasbourg - Esplanade

Patryk Ngondo

University of Strasbourg - Architecture et Réactivité de l’ARN

Lorine Debande

University of Strasbourg - Architecture et Réactivité de l’ARN

Elisabeth Njamkepo

University of Paris-Saclay - Institut Pasteur

Brian Ho

University College London - Institute of Structural and Molecular Biology

François-Xavier Weill

University of Paris-Saclay - Institut Pasteur

Benoît S. Marteyn

University of Strasbourg - Architecture et Réactivité de l’ARN

Claire Jenkins

UK Health Security Agency

Kate Baker

University of Liverpool - Department of Clinical Infection, Microbiology and Immunology

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Abstract

Background: Shigella sp. are enteric pathogens which causes >125 million cases of shigellosis globally. S. sonnei accounts for about a quarter of those cases and is increasingly prevalent in industrialising nations. Being an enteric pathogen, S. sonnei benefits from outcompeting gut commensals such as Escherichia coli to establish itself and cause disease. There are numerous mechanisms that bacterial pathogens use to outcompete its rivals including small molecules called colicins. A Type 6 Secretion System (T6SS) was recently described as contributing to E. coli killing in S. sonnei.

Methods: We used Bulk Phenotyping of Epidemiological Replicates (BPER) which combined bacterial Genome Wide Association Studies (bGWAS) and high throughput phenotyping on a collection of S. sonnei surveillance isolates to identify the genetic features associated with E. coli killing and explore their relationship with epidemiological behaviour. We further explored the presence of colicins in the isolates using genomics, laboratory experimentation, and proteomics.

Findings: Our bGWAS analysis returned known and novel colicin and colicin related genes as significantly associated with E. coli killing. In silico analyses identified key colicin clusters responsible for the killing phenotype associated with epidemiologically successful sub-lineages. The killing phenotype was not associated with the presence of a T6SS. Laboratory analyses confirmed the presence of the key colicin clusters and that killing was contact-independent.

Interpretation: Colicins are responsible for E. coli killing by S. sonnei, not a T6SS. This phenotype contributes to shaping the observed epidemiology of S. sonnei and may contribute to its increasing prevalence globally. BPER is an epidemiologically relevant approach to phenotypic testing that enables the rapid identification of genetic drivers of phenotypic changes, and assessment of their relevance to epidemiology in natural settings.

Funding Information: P.M.D.S and K.S.B. are supported by a Biotechnology and Biological Sciences Research Council project grant BB/V009184/1. R.J.B is funded by a Biotechnology and Biological Sciences Research Council Doctoral Training Partnership studentship BB/M011186/1. K.S.B was also supported by a Wellcome Trust Clinical Research Career Development Award 106690/A/14/Z and drew on funding from Medical Research Council MR/R020787/1. The mass spectrometry instrumentation was funded by the LABEX: ANR-10-LABX-0036 NETRNA, a funding from the state managed by the French National Research Agency as part of the investments for the future program.

Declaration of Interests: Authors declare no competing interests.

Keywords: Colicins, E.coli killing, Shigella sonnei, Inter-bacterial competition

Suggested Citation

De Silva, P. Malaka and Bennett, Rebecca J. and Kuhn, Lauriane and Ngondo, Patryk and Debande, Lorine and Njamkepo, Elisabeth and Ho, Brian and Weill, François-Xavier and Marteyn, Benoît S. and Jenkins, Claire and Baker, Kate, Escherichia Coli Killing by Epidemiologically Successful Sublineages of Shigella Sonnei is Mediated by Colicins. Available at SSRN: https://ssrn.com/abstract=4318406 or http://dx.doi.org/10.2139/ssrn.4318406

P. Malaka De Silva

University of Liverpool - Department of Clinical Infection, Microbiology and Immunology ( email )

Rebecca J. Bennett

University of Liverpool - Department of Clinical Infection, Microbiology and Immunology ( email )

Lauriane Kuhn

CNRS - Plateforme Proteomique Strasbourg - Esplanade ( email )

Patryk Ngondo

University of Strasbourg - Architecture et Réactivité de l’ARN ( email )

Lorine Debande

University of Strasbourg - Architecture et Réactivité de l’ARN ( email )

Elisabeth Njamkepo

University of Paris-Saclay - Institut Pasteur ( email )

75724 Paris CEDEX 15
France

Brian Ho

University College London - Institute of Structural and Molecular Biology ( email )

François-Xavier Weill

University of Paris-Saclay - Institut Pasteur ( email )

75724 Paris CEDEX 15
France

Benoît S. Marteyn

University of Strasbourg - Architecture et Réactivité de l’ARN ( email )

Claire Jenkins

UK Health Security Agency ( email )

London
United Kingdom

Kate Baker (Contact Author)

University of Liverpool - Department of Clinical Infection, Microbiology and Immunology ( email )

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