ALPHA-HEMOLYSIN CONTRIBUTES TO THE PATHOGENICITY OF PILIATED DIGALACTOSIDE-BINDING ESCHERICHIA-COLI IN THE KIDNEY - EFFICACY OF AN ALPHA-HEMOLYSIN VACCINE IN PREVENTING RENAL INJURY IN THE BALB/C MOUSE MODEL OF PYELONEPHRITIS
ALPHA-HEMOLYSIN CONTRIBUTES TO THE PATHOGENICITY OF PILIATED DIGALACTOSIDE-BINDING ESCHERICHIA-COLI IN THE KIDNEY - EFFICACY OF AN ALPHA-HEMOLYSIN VACCINE IN PREVENTING RENAL INJURY IN THE BALB/C MOUSE MODEL OF PYELONEPHRITIS
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DOI：
10.1128/iai.59.3.1153-1161.1991
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发表时间：
1991-03-01
影响因子：
3.1
通讯作者：
JI, G
中科院分区：
文献类型：
--
作者：
OHANLEY, P;LALONDE, G;JI, G
大肠杆菌的双半乳糖苷结合 (Gal-Gal) 菌毛和 α-溶血素被认为是人类上行性非梗阻性肾盂肾炎发病机制中的重要毒力决定因素。 通过使用野生型、无毒实验室和遗传定义的粘粒、转化体和重组菌株，在体外和 BALB/c 小鼠肾盂肾炎模型中评估了这些决定因素的致病意义。 体外数据表明，在凝集红细胞的二半乳糖苷结合菌株中，溶血素的溶细胞活性显着增强（P < 0.05）。 溶血增加的基础可能与毒素更有效地递送至宿主质膜中的目标脂质底物有关。 与不表达或仅表达这些决定因素之一的菌株相比，囊内给予表达双半乳糖苷结合和溶血素的细菌通常会导致小鼠更高的死亡率和肾实质损伤。 分析令人信服地证明，二半乳糖苷结合菌毛与上尿路定植相关，溶血素与败血症和肾实质损伤相关。 这些决定因素共同构成了在该模型中产生疾病的最小毒力因子。 还评估了它们作为预防肾盂肾炎疫苗的功效。 纯化的 Gal-Gal 菌毛疫苗可防止（P < 0.05）表现出同源菌毛的攻击野生型菌株随后定植。 溶血素疫苗并没有消除攻击后随后的细菌肾定植，但与盐水对照组相比，它确实保护了（P < 0.05）在攻击后幸存的小鼠免受随后的肾损伤。 这些决定因素的组合也具有保护作用。 Gal-Gal 菌毛和溶血素在疫苗制剂中的组合代表了一种潜在的有价值的策略，通过阻断细菌粘膜感染发病机制中的几个步骤，对肾盂肾炎进行人类免疫预防。
Digalactoside-binding (Gal-Gal) pili and alpha-hemolysin of Escherichia coli have been implicated as important virulence determinants in the pathogenesis of human ascending, nonobstructive pyelonephritis. The pathogenic significance of these determinants was evaluated in vitro and in the BALB/c mouse pyelonephritis model by employing wild-type, avirulent laboratory, and genetically defined cosmids, transformants, and recombinant strains. In vitro data suggest that the cytolytic activity of hemolysin is significantly (P < 0.05) enhanced among digalactoside-binding strains which agglutinate erythrocytes. The basis of increased hemolysis is related presumably to more efficient delivery of the toxin to target lipid substrate in the host plasma membrane. Intravesicular administration of bacteria that express both digalactoside binding and hemolysin generally resulted in greater mortality and renal parenchymal injury in mice than strains that expressed none or only one of these determinants. Analyses convincingly demonstrate that digalactoside-binding pili are corelated with upper urinary tract colonization and that hemolysin is correlated with septicemia and renal parenchymal damage. These determinants collectively constitute the minimal virulence factors to produce disease in this model. Their efficacy as vaccines for the prevention of pyelonephritis was also assessed. A purified Gal-Gal pilus vaccine prevented (P < 0.05) subsequent colonization by a challenge wild-type strain that exhibited homologous pili. The hemolysin vaccine did not abrogate subsequent bacterial renal colonization on challenge, but it did protect (P < 0.05) mice which survived challenge from subsequent renal injury compared with those in the saline control group. The combination of these determinants was also protective. The combination of Gal-Gal pili and hemolysin in a vaccine preparation represents a potentially worthwhile strategy for human immunoprophylaxis against pyelonephritis by interdicting several steps in the pathogenesis of a bacterial mucosal infection.