O'Hanley P, Lark D, Falkow S, Schoolnik G
J Clin Invest. 1985 Feb;75(2):347-60. doi: 10.1172/JCI111707.
Most human pyelonephritis Escherichia coli isolates express both mannose (MS)- and globoside (Gal-Gal)-binding pili. An ascending E. coli urinary tract infection model was established in the 16-wk-old female BALB/c mouse to compare the pathogenic significance of MS and Gal-Gal pili and their efficacy as vaccines for the prevention of pyelonephritis. The distribution and density of pilus receptor compounds in urogenital tissues and as soluble compounds in urine were determined with antibodies to the synthetic receptor analogues, alpha D-Gal(1----4) beta D-Gal and alpha D-Man(1----2) alpha D-Man. Both carbohydrates were detected in vagina, bladder, ureter, and renal pelvis epithelium and in collecting duct and tubular cells. A pilus receptor compound also was detected in urine. It competitively inhibited the binding capacity of MS pili and was found to be physically, chemically, and immunologically related to Tamm-Horsfall uromucoid. Infectivity and invasiveness were quantitatively and histologically characterized for four E. coli strains: J96, a human pyelonephritis strain that expresses both MS and Gal-Gal pili; two recombinant strains prepared from J96 chromosomal DNA encoding MS pili or Gal-Gal pili; and the nonpiliated K12 recipient. Intravesicular administration of J96 (10(6) colony-forming units [CFU]) resulted in renal colonization and invasion in each of nine mice. The Gal-Gal clone (10(6) CFU) colonized the kidneys in each of 10 mice but did not invade. In contrast, the MS clone (10(6) CFU) did not colonize renal epithelium or invade. This effect was superceded when larger doses (greater than or equal to 10(10) CFU) of the MS clone were administered in volumes that cause acute vesicoureteric reflux. The efficacy was determined of vaccines composed of pure MS or Gal-Gal pili or the lipopolysaccharide containing O somatic antigen of the challenge strain, J96. The Gal-Gal pilus vaccine blocked renal colonization in 19 of 22 mice and renal invasion in 10 of 11 mice. Gal-Gal pili may be useful immunogens for the prevention of pyelonephritis in anatomically normal urinary tracts.
大多数人类肾盂肾炎大肠杆菌分离株都表达甘露糖（MS）结合菌毛和糖苷（Gal-Gal）结合菌毛。在16周龄雌性BALB/c小鼠中建立了大肠杆菌上行性尿路感染模型，以比较MS菌毛和Gal-Gal菌毛的致病意义及其作为预防肾盂肾炎疫苗的效果。用针对合成受体类似物α-D-Gal(1→4)β-D-Gal和α-D-Man(1→2)α-D-Man的抗体，测定泌尿生殖组织中菌毛受体化合物的分布和密度以及尿液中可溶性化合物的情况。在阴道、膀胱、输尿管、肾盂上皮以及集合管和肾小管细胞中均检测到这两种碳水化合物。在尿液中也检测到一种菌毛受体化合物。它能竞争性抑制MS菌毛的结合能力，并且在物理、化学和免疫学上与Tamm-Horsfall尿黏蛋白相关。对四株大肠杆菌进行了感染性和侵袭性的定量及组织学特征分析：J96，一株表达MS菌毛和Gal-Gal菌毛的人类肾盂肾炎菌株；由编码MS菌毛或Gal-Gal菌毛的J96染色体DNA制备的两株重组菌株；以及非菌毛化的K12受体菌。膀胱内接种J96（10⁶菌落形成单位[CFU]）导致9只小鼠中的每只都出现肾脏定植和侵袭。Gal-Gal克隆株（10⁶CFU）使10只小鼠中的每只都出现肾脏定植，但未发生侵袭。相比之下，MS克隆株（10⁶CFU）未在肾上皮定植或侵袭。当以导致急性膀胱输尿管反流的体积给予更大剂量（大于或等于10¹⁰CFU）的MS克隆株时，这种效应被取代。测定了由纯MS菌毛或Gal-Gal菌毛或含有攻击菌株J96的O菌体抗原的脂多糖组成的疫苗的效果。Gal-Gal菌毛疫苗在22只小鼠中的19只中阻止了肾脏定植，在11只小鼠中的10只中阻止了肾脏侵袭。Gal-Gal菌毛可能是预防解剖结构正常的尿路肾盂肾炎的有用免疫原。
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