Characterization of Saa, a novel autoagglutinating adhesin produced by locus of enterocyte effacement-negative shiga-toxigenic Escherichia coli strains that are virulent for humans
Characterization of Saa, a novel autoagglutinating adhesin produced by locus of enterocyte effacement-negative shiga-toxigenic Escherichia coli strains that are virulent for humans
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DOI：
10.1128/iai.69.11.6999-7009.2001
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发表时间：
2001-11-01
影响因子：
3.1
通讯作者：
Paton, JC
中科院分区：
文献类型：
--
作者：
Paton, AW;Srimanote, P;Paton, JC
滋贺菌致突变大肠杆菌（STEC）粘附于肠粘膜的能力无疑与人类疾病的发病有关。从严重病例中分离的大多数STEC菌株在肠粘膜上产生附着和消退性损伤，这是由肠上皮细胞消退（LEE）致病岛位点介导的特性。该元素对于发病机制不是必需的，因为一些严重疾病的病例，包括溶血性尿毒综合征（HUS），是由LEE阴性STEC菌株引起的，但是这些粘附到肠粘膜的机制尚不清楚。我们已经从导致HUS爆发的LEE阴性O 113：H21 STEC菌株（98 NK 2）的大质粒中分离出一个基因，该基因编码一种称为Saa（STEC autoagglutinating adhesin）的自凝集粘附素。在pBC中克隆的saa的引入导致E. coliJM 109对HEp-2细胞的粘附性和半定位粘附模式。在98 NK 2中突变saa，或治愈其大质粒的野生型菌株，导致粘附显著减少。在几种不相关的LEE阴性STEC血清型中发现了saa的同源物，包括O 48：H21（菌株94 CR）和O 91：H21（菌株B2 F1），它们也从HUS患者中分离出来。Saa与小肠结肠炎耶尔森氏菌的YadA和最近描述的来自大肠杆菌的噬菌体编码的免疫球蛋白结合蛋白Eib具有低程度的相似性（25%氨基酸[aa]同一性）。杆菌由98 NK 2产生的Saa长516个氨基酸，包括4个拷贝的37个氨基酸的直接重复序列。有趣的是，由其他STEC菌株产生的Saa的大小范围为460至534 aa，这是由于紧邻重复结构域的重复数量和/或其他插入或缺失的变化。
The capacity of Shiga toxigenic Escherichia coli (STEC) to adhere to the intestinal mucosa undoubtedly contributes to pathogenesis of human disease. The majority of STEC strains isolated from severe cases produce attaching and effacing lesions on the intestinal mucosa, a property mediated by the locus of enterocyte effacement (LEE) pathogenicity island. This element is not essential for pathogenesis, as some cases of severe disease, including hemolytic uremic syndrome (HUS), are caused by LEE-negative STEC strains, but the mechanism whereby these adhere to the intestinal mucosa is not understood. We have isolated a gene from the megaplasmid of a LEE-negative O113:H21 STEC strain (98NK2) responsible for an outbreak of HUS, which encodes an auto-agglutinating adhesin designated Saa (STEC autoagglutinating adhesin). Introduction of saa cloned in pBC results in a 9.7-fold increase in adherence of E. coli JM109 to HEp-2 cells and a semilocalized adherence pattern. Mutagenesis of saa in 98NK2, or curing the wild-type strain of its megaplasmid, resulted in a significant reduction in adherence. Homologues of saa were found in several unrelated LEE-negative STEC serotypes, including O48:H21 (strain 94CR) and O91:H21 (strain B2F1), which were also isolated from patients with HUS. Saa exhibits a low degree of similarity (25% amino acid [aa] identity) with YadA of Yersinia enterocolitica and Eib, a recently described phage-encoded immunoglobulin binding protein from E. coli. Saa produced by 98NK2 is 516 aa long and includes four copies of a 37-aa direct repeat sequence. Interestingly, Saa produced by other STEC strains ranges in size from 460 to 534 aa as a consequence of variation in the number of repeats and/or other insertions or deletions immediately proximal to the repeat domain.