Novartis Vaccines and Diagnostics, 53100 Siena, Italy.
Proc Natl Acad Sci U S A. 2010 May 18;107(20):9072-7. doi: 10.1073/pnas.0915077107. Epub 2010 May 3.
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.
肠外致病性大肠杆菌（ExPEC）是哺乳动物和鸟类疾病的常见病因。鉴于这些细菌的抗生素耐药性不断增加，预防此类感染的疫苗将是理想的选择。我们已经确定了从新生儿脑膜炎病例中分离出的 ExPEC IHE3034（ST95）的基因组序列，并将其与其他 ExPEC 菌株和一些非致病性大肠杆菌的可用基因组序列进行了比较。我们发现 IHE3034 基因组中存在 19 个基因组岛，而这些基因组岛不存在于非致病性大肠杆菌分离株中。通过使用减法反向疫苗学，我们鉴定出 230 种存在于 ExPEC 但不存在（或存在低相似性）于非致病性菌株中的抗原。在小鼠攻毒模型中，有 9 种抗原具有保护作用。其中一些抗原也存在于其他致病性非 ExPEC 菌株中，这表明可能开发出一种广泛保护性的大肠杆菌疫苗。大多数大肠杆菌分离株中都检测到编码最具保护性抗原的基因，该基因在序列上高度保守，并发现通过 II 型分泌系统进行输出，而该系统在非致病性菌株中似乎不起作用。
