The Polyamine Spermidine Modulates the Production of the Bacterial Genotoxin Colibactin.

Autor:	Chagneau CV; CHU Toulouse, Service de Bactériologie-Hygiène, Toulouse, France.; IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, France., Garcie C; CHU Toulouse, Service de Bactériologie-Hygiène, Toulouse, France.; IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, France., Bossuet-Greif N; IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, France., Tronnet S; IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, France., Brachmann AO; Institute of Microbiology, Eidgenössische Technische Hochschule (ETH), Zurich, Switzerland., Piel J; Institute of Microbiology, Eidgenössische Technische Hochschule (ETH), Zurich, Switzerland., Nougayrède JP; IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, France., Martin P; IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, France., Oswald E; CHU Toulouse, Service de Bactériologie-Hygiène, Toulouse, France eric.oswald@inserm.fr.; IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, France.
Jazyk:	angličtina
Zdroj:	MSphere [mSphere] 2019 Oct 02; Vol. 4 (5). Date of Electronic Publication: 2019 Oct 02.
DOI:	10.1128/mSphere.00414-19
Abstrakt:	Colibactin is a polyketide/nonribosomal peptide produced by Escherichia coli strains that harbor the pks island. This toxin induces DNA double-strand breaks and DNA interstrand cross-links in infected eukaryotic cells. Colibactin-producing strains are found associated with colorectal cancer biopsy specimens and promote intestinal tumor progression in various murine models. Polyamines are small polycationic molecules produced by both microorganisms and eukaryotic cells. Their levels are increased in malignancies, where they contribute to disease progression and metastasis. In this study, we demonstrated that the endogenous spermidine synthase SpeE is required for full genotoxic activity of colibactin-producing E. coli Supplying spermidine in a Δ speE pks + E. coli strain restored genotoxic activity. Spermidine is involved in the autotoxicity linked to colibactin and is required for direct damaging activity on DNA. The production of the colibactin prodrug motif is impaired in Δ speE mutants. Therefore, we demonstrated that spermidine has a direct impact on colibactin synthesis. IMPORTANCE Colibactin-producing Escherichia coli strains are associated with cancerous and precancerous colorectal tissues and are suspected of promoting colorectal carcinogenesis. In this study, we describe a new interplay between the synthesis of the genotoxin colibactin and the polyamine spermidine. Polyamines are highly abundant in cancer tissue and are associated with cell proliferation. The need for spermidine in genotoxic activity provides a new perspective on the role of these metabolites in the pathogenicity of colibactin-producing E. coli strains in colorectal cancer. (Copyright © 2019 Chagneau et al.)
Databáze:	MEDLINE
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