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The Genotoxin Colibactin is a Determinant of Virulence in Escherichia coli K1 Experimental Neonatal Systemic Infection

McCarthy, AJ; Martin, P; Cloup, E; Stabler, R; Oswald, E; Taylor, PW; (2015) The Genotoxin Colibactin is a Determinant of Virulence in Escherichia coli K1 Experimental Neonatal Systemic Infection. Infection and Immunity , 83 (9) pp. 3704-3711. 10.1128/IAI.00716-15. Green open access

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Abstract

Escherichia coli expressing the K1 capsule are a major cause of sepsis and meningitis in human neonates. The development of these diseases is dependent on the expression of a range of virulence factors, many of which remain uncharacterised. Here, we show that all but one of 34 E. coli K1 neonatal isolates carry clbA and clbP, genes contained within the pks pathogenicity island and required for the synthesis of colibactin, a polyketide-peptide genotoxin that causes genomic instability in eukaryotic cells by induction of double-strand breaks in DNA. Inactivation of clbA and clbP in E. coli A192PP, a virulent strain of serotype O18:K1 that colonizes the gastrointestinal tract and translocates to the blood compartment with very high frequency in experimental infection of the neonatal rat, significantly reduced the capacity of A192PP to colonize the gut, engender double-strand breaks in DNA and cause invasive, lethal disease. Mutation of clbA, which encodes a pleiotropic enzyme also involved in siderophore synthesis, impacted virulence to a greater extent than mutation of clbP, encoding an enzyme specific to colibactin synthesis. Restoration of colibactin gene function by complementation re-established the fully virulent phenotype. We conclude that colibactin contributes to the capacity of E. coli K1 to colonise the neonatal gastrointestinal tract and to cause invasive disease in the susceptible neonate.

Type: Article
Title: The Genotoxin Colibactin is a Determinant of Virulence in Escherichia coli K1 Experimental Neonatal Systemic Infection
Open access status: An open access version is available from UCL Discovery
DOI: 10.1128/IAI.00716-15
Publisher version: http://dx.doi.org/10.1128/IAI.00716-15
Language: English
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics
URI: https://discovery.ucl.ac.uk/id/eprint/1469901
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