科學家發(fā)現(xiàn)了可能用于預防埃希氏大腸桿菌(E. coli)感染的廣譜疫苗的細菌成分,。Rino Rappuoli及其同事比較了已知會導致新生兒腦膜炎的大腸桿菌以及其他致病和非致病大腸桿菌的基因組,。這組科學家發(fā)現(xiàn)了僅在致病菌株中表達的230個蛋白質,它們可能用于防止細菌感染,, 然后他們?yōu)樾∈笞⑸淞诉@些蛋白質,。在讓這些小鼠接觸了致命劑量的致病大腸桿菌之后,這組科學家發(fā)現(xiàn)其中9種蛋白質防止了小鼠的感染,。
大腸桿菌是人類消化道中的一種常見定居者,,盡管大多數(shù)感染是溫和的,致病菌株占了尿道感染病例的80%以上,,而且是新生兒腦膜炎和血液中毒的第二大病因,。大腸桿菌菌株的遺傳結構有很大的差異,這妨礙了研發(fā)大腸桿菌疫苗的傳統(tǒng)方法,。這組作者說,,該研究發(fā)現(xiàn)的這9種抗原的遺傳標記保存在幾種致病大腸桿菌菌株中,而把這些抗原的一種或幾種結合起來有可能研發(fā)出具有廣泛保護作用的大腸桿菌疫苗,。(生物谷Bioon.com)
生物谷推薦原文出處:
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.