FdeC, a Novel Broadly Conserved <named-content content-type="genus-species">Escherichia coli</named-content> Adhesin Eliciting Protection against Urinary Tract Infections

ABSTRACT The increasing antibiotic resistance of pathogenic Escherichia coli species and the absence of a pan-protective vaccine pose major health concerns. We recently identified, by subtractive reverse vaccinology, nine Escherichia coli antigens that protect mice from sepsis. In this study, we cha...

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Autores principales:	Barbara Nesta, Glen Spraggon, Christopher Alteri, Danilo Gomes Moriel, Roberto Rosini, Daniele Veggi, Sara Smith, Isabella Bertoldi, Ilaria Pastorello, Ilaria Ferlenghi, Maria Rita Fontana, Gad Frankel, Harry L. T. Mobley, Rino Rappuoli, Mariagrazia Pizza, Laura Serino, Marco Soriani
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2012
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/2b6beac9d4a94422bfcf7290d1fa17a3
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spelling	oai:doaj.org-article:2b6beac9d4a94422bfcf7290d1fa17a32021-11-15T15:39:09ZFdeC, a Novel Broadly Conserved <named-content content-type="genus-species">Escherichia coli</named-content> Adhesin Eliciting Protection against Urinary Tract Infections10.1128/mBio.00010-122150-7511https://doaj.org/article/2b6beac9d4a94422bfcf7290d1fa17a32012-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00010-12https://doaj.org/toc/2150-7511ABSTRACT The increasing antibiotic resistance of pathogenic Escherichia coli species and the absence of a pan-protective vaccine pose major health concerns. We recently identified, by subtractive reverse vaccinology, nine Escherichia coli antigens that protect mice from sepsis. In this study, we characterized one of them, ECOK1_0290, named FdeC (factor adherence E. coli) for its ability to mediate E. coli adhesion to mammalian cells and extracellular matrix. This adhesive propensity was consistent with the X-ray structure of one of the FdeC domains that shows a striking structural homology to Yersinia pseudotuberculosis invasin and enteropathogenic E. coli intimin. Confocal imaging analysis revealed that expression of FdeC on the bacterial surface is triggered by interaction of E. coli with host cells. This phenotype was also observed in bladder tissue sections derived from mice infected with an extraintestinal strain. Indeed, we observed that FdeC contributes to colonization of the bladder and kidney, with the wild-type strain outcompeting the fdeC mutant in cochallenge experiments. Finally, intranasal mucosal immunization with recombinant FdeC significantly reduced kidney colonization in mice challenged transurethrally with uropathogenic E. coli, supporting a role for FdeC in urinary tract infections. IMPORTANCE Pathogenic Escherichia coli strains are involved in a diverse spectrum of diseases, including intestinal and extraintestinal infections (urinary tract infections and sepsis). The absence of a broadly protective vaccine against all these E. coli strains is a major problem for modern society due to high costs to health care systems. Here, we describe the structural and functional properties of a recently reported protective antigen, named FdeC, and elucidated its putative role during extraintestinal pathogenic E. coli infection by using both in vitro and in vivo infection models. The conservation of FdeC among strains of different E. coli pathotypes highlights its potential as a component of a broadly protective vaccine against extraintestinal and intestinal E. coli infections.Barbara NestaGlen SpraggonChristopher AlteriDanilo Gomes MorielRoberto RosiniDaniele VeggiSara SmithIsabella BertoldiIlaria PastorelloIlaria FerlenghiMaria Rita FontanaGad FrankelHarry L. T. MobleyRino RappuoliMariagrazia PizzaLaura SerinoMarco SorianiAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 3, Iss 2 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Barbara Nesta Glen Spraggon Christopher Alteri Danilo Gomes Moriel Roberto Rosini Daniele Veggi Sara Smith Isabella Bertoldi Ilaria Pastorello Ilaria Ferlenghi Maria Rita Fontana Gad Frankel Harry L. T. Mobley Rino Rappuoli Mariagrazia Pizza Laura Serino Marco Soriani FdeC, a Novel Broadly Conserved <named-content content-type="genus-species">Escherichia coli</named-content> Adhesin Eliciting Protection against Urinary Tract Infections
description	ABSTRACT The increasing antibiotic resistance of pathogenic Escherichia coli species and the absence of a pan-protective vaccine pose major health concerns. We recently identified, by subtractive reverse vaccinology, nine Escherichia coli antigens that protect mice from sepsis. In this study, we characterized one of them, ECOK1_0290, named FdeC (factor adherence E. coli) for its ability to mediate E. coli adhesion to mammalian cells and extracellular matrix. This adhesive propensity was consistent with the X-ray structure of one of the FdeC domains that shows a striking structural homology to Yersinia pseudotuberculosis invasin and enteropathogenic E. coli intimin. Confocal imaging analysis revealed that expression of FdeC on the bacterial surface is triggered by interaction of E. coli with host cells. This phenotype was also observed in bladder tissue sections derived from mice infected with an extraintestinal strain. Indeed, we observed that FdeC contributes to colonization of the bladder and kidney, with the wild-type strain outcompeting the fdeC mutant in cochallenge experiments. Finally, intranasal mucosal immunization with recombinant FdeC significantly reduced kidney colonization in mice challenged transurethrally with uropathogenic E. coli, supporting a role for FdeC in urinary tract infections. IMPORTANCE Pathogenic Escherichia coli strains are involved in a diverse spectrum of diseases, including intestinal and extraintestinal infections (urinary tract infections and sepsis). The absence of a broadly protective vaccine against all these E. coli strains is a major problem for modern society due to high costs to health care systems. Here, we describe the structural and functional properties of a recently reported protective antigen, named FdeC, and elucidated its putative role during extraintestinal pathogenic E. coli infection by using both in vitro and in vivo infection models. The conservation of FdeC among strains of different E. coli pathotypes highlights its potential as a component of a broadly protective vaccine against extraintestinal and intestinal E. coli infections.
format	article
author	Barbara Nesta Glen Spraggon Christopher Alteri Danilo Gomes Moriel Roberto Rosini Daniele Veggi Sara Smith Isabella Bertoldi Ilaria Pastorello Ilaria Ferlenghi Maria Rita Fontana Gad Frankel Harry L. T. Mobley Rino Rappuoli Mariagrazia Pizza Laura Serino Marco Soriani
author_facet	Barbara Nesta Glen Spraggon Christopher Alteri Danilo Gomes Moriel Roberto Rosini Daniele Veggi Sara Smith Isabella Bertoldi Ilaria Pastorello Ilaria Ferlenghi Maria Rita Fontana Gad Frankel Harry L. T. Mobley Rino Rappuoli Mariagrazia Pizza Laura Serino Marco Soriani
author_sort	Barbara Nesta
title	FdeC, a Novel Broadly Conserved <named-content content-type="genus-species">Escherichia coli</named-content> Adhesin Eliciting Protection against Urinary Tract Infections
title_short	FdeC, a Novel Broadly Conserved <named-content content-type="genus-species">Escherichia coli</named-content> Adhesin Eliciting Protection against Urinary Tract Infections
title_full	FdeC, a Novel Broadly Conserved <named-content content-type="genus-species">Escherichia coli</named-content> Adhesin Eliciting Protection against Urinary Tract Infections
title_fullStr	FdeC, a Novel Broadly Conserved <named-content content-type="genus-species">Escherichia coli</named-content> Adhesin Eliciting Protection against Urinary Tract Infections
title_full_unstemmed	FdeC, a Novel Broadly Conserved <named-content content-type="genus-species">Escherichia coli</named-content> Adhesin Eliciting Protection against Urinary Tract Infections
title_sort	fdec, a novel broadly conserved <named-content content-type="genus-species">escherichia coli</named-content> adhesin eliciting protection against urinary tract infections
publisher	American Society for Microbiology
publishDate	2012
url	https://doaj.org/article/2b6beac9d4a94422bfcf7290d1fa17a3
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FdeC, a Novel Broadly Conserved <named-content content-type="genus-species">Escherichia coli</named-content> Adhesin Eliciting Protection against Urinary Tract Infections

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