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Identification of protective and broadly conserved vaccine antigens from the genome of extraintestinal pathogenic Escherichia coli. 2010
Danilo Gomes Moriel, and
Isabella Bertoldi, and
Angela Spagnuolo, and
Sara Marchi, and
Roberto Rosini, and
Barbara Nesta, and
Ilaria Pastorello, and
Vanja A Mariani Corea, and
Giulia Torricelli, and
Elena Cartocci, and
Silvana Savino, and
Maria Scarselli, and
Ulrich Dobrindt, and
Jörg Hacker, and
Hervé Tettelin, and
Luke J Tallon, and
Steven Sullivan, and
Lothar H Wieler, and
Christa Ewers, and
Derek Pickard, and
Gordon Dougan, and
Maria Rita Fontana, and
Rino Rappuoli, and
Mariagrazia Pizza, and
Laura Serino
Novartis Vaccines and Diagnostics, 53100 Siena, Italy.
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.
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Maria Scarselli, and
Ulrich Dobrindt, and
Jörg Hacker, and
Hervé Tettelin, and
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Christa Ewers, and
Derek Pickard, and
Gordon Dougan, and
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