Interplay between siderophores and colibactin genotoxin biosynthetic pathways in Escherichia coli.

In Escherichia coli, the biosynthetic pathways of several small iron-scavenging molecules known as siderophores (enterobactin, salmochelins and yersiniabactin) and of a genotoxin (colibactin) are known to require a 4'-phosphopantetheinyl transferase (PPTase). Only two PPTases have been clearly...

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Autores principales:	Patricia Martin, Ingrid Marcq, Giuseppe Magistro, Marie Penary, Christophe Garcie, Delphine Payros, Michèle Boury, Maïwenn Olier, Jean-Philippe Nougayrède, Marc Audebert, Christian Chalut, Sören Schubert, Eric Oswald
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/a1884c7b1e144e7b8e02e9a80d518060
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spelling	oai:doaj.org-article:a1884c7b1e144e7b8e02e9a80d5180602021-11-18T06:05:24ZInterplay between siderophores and colibactin genotoxin biosynthetic pathways in Escherichia coli.1553-73661553-737410.1371/journal.ppat.1003437https://doaj.org/article/a1884c7b1e144e7b8e02e9a80d5180602013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23853582/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374In Escherichia coli, the biosynthetic pathways of several small iron-scavenging molecules known as siderophores (enterobactin, salmochelins and yersiniabactin) and of a genotoxin (colibactin) are known to require a 4'-phosphopantetheinyl transferase (PPTase). Only two PPTases have been clearly identified: EntD and ClbA. The gene coding for EntD is part of the core genome of E. coli, whereas ClbA is encoded on the pks pathogenicity island which codes for colibactin. Interestingly, the pks island is physically associated with the high pathogenicity island (HPI) in a subset of highly virulent E. coli strains. The HPI carries the gene cluster required for yersiniabactin synthesis except for a gene coding its cognate PPTase. Here we investigated a potential interplay between the synthesis pathways leading to the production of siderophores and colibactin, through a functional interchangeability between EntD and ClbA. We demonstrated that ClbA could contribute to siderophores synthesis. Inactivation of both entD and clbA abolished the virulence of extra-intestinal pathogenic E. coli (ExPEC) in a mouse sepsis model, and the presence of either functional EntD or ClbA was required for the survival of ExPEC in vivo. This is the first report demonstrating a connection between multiple phosphopantetheinyl-requiring pathways leading to the biosynthesis of functionally distinct secondary metabolites in a given microorganism. Therefore, we hypothesize that the strict association of the pks island with HPI has been selected in highly virulent E. coli because ClbA is a promiscuous PPTase that can contribute to the synthesis of both the genotoxin and siderophores. The data highlight the complex regulatory interaction of various virulence features with different functions. The identification of key points of these networks is not only essential to the understanding of ExPEC virulence but also an attractive and promising target for the development of anti-virulence therapy strategies.Patricia MartinIngrid MarcqGiuseppe MagistroMarie PenaryChristophe GarcieDelphine PayrosMichèle BouryMaïwenn OlierJean-Philippe NougayrèdeMarc AudebertChristian ChalutSören SchubertEric OswaldPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 7, p e1003437 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Patricia Martin Ingrid Marcq Giuseppe Magistro Marie Penary Christophe Garcie Delphine Payros Michèle Boury Maïwenn Olier Jean-Philippe Nougayrède Marc Audebert Christian Chalut Sören Schubert Eric Oswald Interplay between siderophores and colibactin genotoxin biosynthetic pathways in Escherichia coli.
description	In Escherichia coli, the biosynthetic pathways of several small iron-scavenging molecules known as siderophores (enterobactin, salmochelins and yersiniabactin) and of a genotoxin (colibactin) are known to require a 4'-phosphopantetheinyl transferase (PPTase). Only two PPTases have been clearly identified: EntD and ClbA. The gene coding for EntD is part of the core genome of E. coli, whereas ClbA is encoded on the pks pathogenicity island which codes for colibactin. Interestingly, the pks island is physically associated with the high pathogenicity island (HPI) in a subset of highly virulent E. coli strains. The HPI carries the gene cluster required for yersiniabactin synthesis except for a gene coding its cognate PPTase. Here we investigated a potential interplay between the synthesis pathways leading to the production of siderophores and colibactin, through a functional interchangeability between EntD and ClbA. We demonstrated that ClbA could contribute to siderophores synthesis. Inactivation of both entD and clbA abolished the virulence of extra-intestinal pathogenic E. coli (ExPEC) in a mouse sepsis model, and the presence of either functional EntD or ClbA was required for the survival of ExPEC in vivo. This is the first report demonstrating a connection between multiple phosphopantetheinyl-requiring pathways leading to the biosynthesis of functionally distinct secondary metabolites in a given microorganism. Therefore, we hypothesize that the strict association of the pks island with HPI has been selected in highly virulent E. coli because ClbA is a promiscuous PPTase that can contribute to the synthesis of both the genotoxin and siderophores. The data highlight the complex regulatory interaction of various virulence features with different functions. The identification of key points of these networks is not only essential to the understanding of ExPEC virulence but also an attractive and promising target for the development of anti-virulence therapy strategies.
format	article
author	Patricia Martin Ingrid Marcq Giuseppe Magistro Marie Penary Christophe Garcie Delphine Payros Michèle Boury Maïwenn Olier Jean-Philippe Nougayrède Marc Audebert Christian Chalut Sören Schubert Eric Oswald
author_facet	Patricia Martin Ingrid Marcq Giuseppe Magistro Marie Penary Christophe Garcie Delphine Payros Michèle Boury Maïwenn Olier Jean-Philippe Nougayrède Marc Audebert Christian Chalut Sören Schubert Eric Oswald
author_sort	Patricia Martin
title	Interplay between siderophores and colibactin genotoxin biosynthetic pathways in Escherichia coli.
title_short	Interplay between siderophores and colibactin genotoxin biosynthetic pathways in Escherichia coli.
title_full	Interplay between siderophores and colibactin genotoxin biosynthetic pathways in Escherichia coli.
title_fullStr	Interplay between siderophores and colibactin genotoxin biosynthetic pathways in Escherichia coli.
title_full_unstemmed	Interplay between siderophores and colibactin genotoxin biosynthetic pathways in Escherichia coli.
title_sort	interplay between siderophores and colibactin genotoxin biosynthetic pathways in escherichia coli.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/a1884c7b1e144e7b8e02e9a80d518060
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Interplay between siderophores and colibactin genotoxin biosynthetic pathways in Escherichia coli.

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