科学家发现了可能用于预防埃希氏大肠杆菌（E. coli）感染的广谱疫苗的细菌成分。Rino Rappuoli及其同事比较了已知会导致新生儿脑膜炎的大肠杆菌以及其他致病和非致病大肠杆菌的基因组。这组科学家发现了仅在致病菌株中表达的230个蛋白质，它们可能用于防止细菌感染， 然后他们为小鼠注射了这些蛋白质。在让这些小鼠接触了致命剂量的致病大肠杆菌之后，这组科学家发现其中9种蛋白质防止了小鼠的感染。
大肠杆菌是人类消化道中的一种常见定居者，尽管大多数感染是温和的，致病菌株占了尿道感染病例的80%以上，而且是新生儿脑膜炎和血液中毒的第二大病因。大肠杆菌菌株的遗传结构有很大的差异，这妨碍了研发大肠杆菌疫苗的传统方法。这组作者说，该研究发现的这9种抗原的遗传标记保存在几种致病大肠杆菌菌株中，而把这些抗原的一种或几种结合起来有可能研发出具有广泛保护作用的大肠杆菌疫苗。
原文出处：
PNAS doi: 10.1073/pnas.0915077107
Identification of protective and broadly conserved vaccine antigens from the genome of extraintestinal pathogenic Escherichia coli
Danilo Gomes Moriela, Isabella Bertoldia, Angela Spagnuoloa, Sara Marchia, Roberto Rosinia, Barbara Nestaa, Ilaria Pastorelloa, Vanja A. Mariani Coreaa, Giulia Torricellia, Elena Cartoccia, Silvana Savinoa, Maria Scarsellia, Ulrich Dobrindtb, J?rg Hackerb,c, Hervé Tettelind,2, Luke J. Tallond,2, Steven Sullivand,3, Lothar H. Wielere, Christa Ewerse, Derek Pickardf, Gordon Douganf, Maria Rita Fontanaa, Rino Rappuolia,1, Mariagrazia Pizzaa, and Laura Serinoa,1
aNovartis Vaccines and Diagnostics, 53100 Siena, Italy;
bInstitut für Molekulare Infektionsbiologie, Universit?t Würzburg, D-97080 Würzburg, Germany;
cGerman Academy of Sciences Leopoldina, D-06108 Halle, Germany;
dJ. Craig Venter Institute, Rockville, MD 20850;
eInstitut für Mikrobiologie und Tierseuchen, Freie Universit?t Berlin, D-10061 Berlin, Germany; and
fWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK
?2Current address: Institute for Genome Sciences, School of Medicine, University of Maryland, Baltimore, MD 21201.
?3School of Medicine, New York University, New York, NY 10010.
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.
