The Polyamine Spermidine Modulates the Production of the Bacterial Genotoxin Colibactin

ABSTRACT 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...

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Autores principales:	Camille V. Chagneau, Christophe Garcie, Nadège Bossuet-Greif, Sophie Tronnet, Alexander O. Brachmann, Jörn Piel, Jean-Philippe Nougayrède, Patricia Martin, Eric Oswald
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Escherichia coli biosynthesis colorectal cancer genotoxic colibactin polyamines Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/f385369a64724228830f1876acd7b499
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spelling	oai:doaj.org-article:f385369a64724228830f1876acd7b4992021-11-15T15:27:32ZThe Polyamine Spermidine Modulates the Production of the Bacterial Genotoxin Colibactin10.1128/mSphere.00414-192379-5042https://doaj.org/article/f385369a64724228830f1876acd7b4992019-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00414-19https://doaj.org/toc/2379-5042ABSTRACT 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 ΔspeE 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 ΔspeE 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.Camille V. ChagneauChristophe GarcieNadège Bossuet-GreifSophie TronnetAlexander O. BrachmannJörn PielJean-Philippe NougayrèdePatricia MartinEric OswaldAmerican Society for MicrobiologyarticleEscherichia colibiosynthesiscolorectal cancergenotoxic colibactinpolyaminesMicrobiologyQR1-502ENmSphere, Vol 4, Iss 5 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Escherichia coli biosynthesis colorectal cancer genotoxic colibactin polyamines Microbiology QR1-502
spellingShingle	Escherichia coli biosynthesis colorectal cancer genotoxic colibactin polyamines Microbiology QR1-502 Camille V. Chagneau Christophe Garcie Nadège Bossuet-Greif Sophie Tronnet Alexander O. Brachmann Jörn Piel Jean-Philippe Nougayrède Patricia Martin Eric Oswald The Polyamine Spermidine Modulates the Production of the Bacterial Genotoxin Colibactin
description	ABSTRACT 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 ΔspeE 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 ΔspeE 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.
format	article
author	Camille V. Chagneau Christophe Garcie Nadège Bossuet-Greif Sophie Tronnet Alexander O. Brachmann Jörn Piel Jean-Philippe Nougayrède Patricia Martin Eric Oswald
author_facet	Camille V. Chagneau Christophe Garcie Nadège Bossuet-Greif Sophie Tronnet Alexander O. Brachmann Jörn Piel Jean-Philippe Nougayrède Patricia Martin Eric Oswald
author_sort	Camille V. Chagneau
title	The Polyamine Spermidine Modulates the Production of the Bacterial Genotoxin Colibactin
title_short	The Polyamine Spermidine Modulates the Production of the Bacterial Genotoxin Colibactin
title_full	The Polyamine Spermidine Modulates the Production of the Bacterial Genotoxin Colibactin
title_fullStr	The Polyamine Spermidine Modulates the Production of the Bacterial Genotoxin Colibactin
title_full_unstemmed	The Polyamine Spermidine Modulates the Production of the Bacterial Genotoxin Colibactin
title_sort	polyamine spermidine modulates the production of the bacterial genotoxin colibactin
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/f385369a64724228830f1876acd7b499
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The Polyamine Spermidine Modulates the Production of the Bacterial Genotoxin Colibactin

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