Denich K, Blyn L B, Craiu A, Braaten B A, Hardy J, Low D A, O'Hanley P D
Department of Medicine, Stanford University, California 94305.
Infect Immun. 1991 Nov;59(11):3849-58. doi: 10.1128/iai.59.11.3849-3858.1991.
Pyelonephritis-associated pili (Pap) are important in the pathogenesis of ascending, unobstructive Escherichia coli-caused renal infections because these surface bacterial organelles mediate digalactoside-specific binding to host uroepithelial cells. Pap are composed of many different polypeptides, of which only the tip proteins mediate specific binding. The PapA moiety polymerizes to form the bulk of the pilus structure and has been employed in vaccines despite its lack of Gal alpha(1-4)Gal receptor specificity. Animal recipients of PapA pilus-based vaccines are protected against experimental pyelonephritis caused by homologous and heterologous Gal-Gal-binding uropathogenic E. coli strains. Specific PapA immunoglobulin G antibodies in urine are correlated with protection in these infection models. The nucleotide sequences of the gene encoding PapA were determined for three E. coli clones expressing F7(1), F7(2), and F9 pili and were compared with corresponding sequences for other F serotypes. Specific rabbit antisera were employed in enzyme-linked immunosorbent assays to study the cross-reactivity between Gal-Gal pili purified from recombinant strains expressing F7(1), F7(2), F9, or F13 pili and among 60 Gal-Gal-binding wild-type strains. We present data which corroborate the concept that papA genes are highly homologous and encode proteins which exhibit greater than 70% homology among pili of different serotypes. The differences primarily occur in the cysteine-cysteine loop and variable regions and constitute the basis for serological diversity of these pili. Although there are differences in primary structures among these pili, antisera raised against pili of one serotype cross-reacted frequently with many other Gal-Gal pili of different serotypes. Furthermore, antisera raised against pili of the F13 serotype cross-reacted strongly or moderately with 52 (86%) of 60 wild-type Gal-Gal-binding E. coli strains. These data suggest that there are common immunogenic domains among these proteins. These additional data further support the hypothesis that broadly cross-protective PapA pilus vaccines for the immunoprophylaxis of pyelonephritis might be developed.
肾盂肾炎相关菌毛（Pap）在由上行性、非梗阻性大肠杆菌引起的肾脏感染的发病机制中起着重要作用，因为这些细菌表面细胞器介导了与宿主尿道上皮细胞的二半乳糖苷特异性结合。Pap由许多不同的多肽组成，其中只有顶端蛋白介导特异性结合。PapA部分聚合形成菌毛结构的主体，尽管它缺乏Galα(1-4)Gal受体特异性，但已被用于疫苗中。基于PapA菌毛的疫苗的动物接受者可免受同源和异源Gal-Gal结合尿路致病性大肠杆菌菌株引起的实验性肾盂肾炎的侵害。尿液中的特异性PapA免疫球蛋白G抗体与这些感染模型中的保护作用相关。测定了表达F7(1)、F7(2)和F9菌毛的三个大肠杆菌克隆中编码PapA的基因的核苷酸序列，并与其他F血清型的相应序列进行了比较。使用特异性兔抗血清进行酶联免疫吸附测定，以研究从表达F7(1)、F7(2)、F9或F13菌毛的重组菌株中纯化的Gal-Gal菌毛之间以及60株Gal-Gal结合野生型菌株之间的交叉反应性。我们提供的数据证实了这样一个概念，即papA基因高度同源，编码的蛋白质在不同血清型的菌毛之间具有大于70%的同源性。差异主要发生在半胱氨酸-半胱氨酸环和可变区，构成了这些菌毛血清学多样性的基础。尽管这些菌毛的一级结构存在差异，但针对一种血清型菌毛产生的抗血清经常与许多其他不同血清型的Gal-Gal菌毛发生交叉反应。此外，针对F13血清型菌毛产生的抗血清与60株野生型Gal-Gal结合大肠杆菌菌株中的52株（86%）发生强或中度交叉反应。这些数据表明这些蛋白质之间存在共同的免疫原性结构域。这些额外的数据进一步支持了这样一种假设，即可能开发出用于肾盂肾炎免疫预防的具有广泛交叉保护作用的PapA菌毛疫苗。
