title: Identification of protective and broadly conserved vaccine antigens from the genome of extraintestinal pathogenic Escherichia coli.
abstract: Extraintestinal pathogenic Escherichia coli (ExPEC) are a common cause of disease in both mammals and birds. A vaccine to prevent such infections would be desirable given the increasing antibiotic resistance of these bacteria. We have determined the genome sequence of ExPEC IHE3034 (ST95) isolated from a case of neonatal meningitis and compared this to available genome sequences of other ExPEC strains and a few nonpathogenic E. coli. We found 19 genomic islands present in the genome of IHE3034, which are absent in the nonpathogenic E. coli isolates. By using subtractive reverse vaccinology we identified 230 antigens present in ExPEC but absent (or present with low similarity) in nonpathogenic strains. Nine antigens were protective in a mouse challenge model. Some of them were also present in other pathogenic non-ExPEC strains, suggesting that a broadly protective E. coli vaccine may be possible. The gene encoding the most protective antigen was detected in most of the E. coli isolates, highly conserved in sequence and found to be exported by a type II secretion system which seems to be nonfunctional in nonpathogenic strains.
authors.affiliation: Novartis Vaccines and Diagnostics, 53100 Siena, Italy.
authors.forename: Danilo Gomes
authors.initials: DG
authors.lastname: Moriel
authors.forename: Isabella
authors.initials: I
authors.lastname: Bertoldi
authors.forename: Angela
authors.initials: A
authors.lastname: Spagnuolo
authors.forename: Sara
authors.initials: S
authors.lastname: Marchi
authors.forename: Roberto
authors.initials: R
authors.lastname: Rosini
authors.forename: Barbara
authors.initials: B
authors.lastname: Nesta
authors.forename: Ilaria
authors.initials: I
authors.lastname: Pastorello
authors.forename: Vanja A Mariani
authors.initials: VA
authors.lastname: Corea
authors.forename: Giulia
authors.initials: G
authors.lastname: Torricelli
authors.forename: Elena
authors.initials: E
authors.lastname: Cartocci
authors.forename: Silvana
authors.initials: S
authors.lastname: Savino
authors.forename: Maria
authors.initials: M
authors.lastname: Scarselli
authors.forename: Ulrich
authors.initials: U
authors.lastname: Dobrindt
authors.forename: Jörg
authors.initials: J
authors.lastname: Hacker
authors.forename: Hervé
authors.initials: H
authors.lastname: Tettelin
authors.forename: Luke J
authors.initials: LJ
authors.lastname: Tallon
authors.forename: Steven
authors.initials: S
authors.lastname: Sullivan
authors.forename: Lothar H
authors.initials: LH
authors.lastname: Wieler
authors.forename: Christa
authors.initials: C
authors.lastname: Ewers
authors.forename: Derek
authors.initials: D
authors.lastname: Pickard
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Fontana
authors.forename: Rino
authors.initials: R
authors.lastname: Rappuoli
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Pizza
authors.forename: Laura
authors.initials: L
authors.lastname: Serino
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics*; D001483:Base Sequence; D019295:Computational Biology; D004926:Escherichia coli / Q000235:genetics* / Q000276:immunology; D004927:Escherichia coli Infections / Q000517:prevention & control*; D022361:Escherichia coli Vaccines / Q000235:genetics*; D005387:Finland; D016680:Genome, Bacterial / Q000235:genetics*; D044404:Genomic Islands / Q000235:genetics; D006801:Humans; D020814:Meningitis, Escherichia coli / Q000382:microbiology*; D051379:Mice; D008969:Molecular Sequence Data; D055571:Secretory Pathway / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: D000942:Antigens, Bacterial; D022361:Escherichia coli Vaccines