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Adhesin of Helicobacter pylon : Identification and therapeutic application

幽门螺杆菌粘附素：鉴定及治疗应用

基本信息

批准号：
09557050
负责人：
SUGANO Kentaro
金额：
$ 7.23万
依托单位：
Jichi Medical School (1998-1999)The University of Tokyo (1997)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09557050/
关键词：
Helicobacter pylori adhesin sulfatide Helicobacter pylori 接着ヘリコバクターピロリ糖脂質

项目摘要

Attachment of Helicobacter pylon (HP) to gastric epithelium is a crucial step for perpetuating the infection. Tight adhesion of the organism to the epithelium profoundly affects the epithelial function causing various diseases. The attachment is mediated by specific bacterial proteins called adhesins which recognize specific receptors. In most cases, cell surface glycoconjugates have been demonstrated as bacterial adhesion receptors. In the case of HP, several putative adhesins with different receptor specificities have been reported. In this project, we tried to identify adhesins which specifically recognize sulfatide. Using two different affimty chromatographies, one with heparin-sepharose and the other with sulfated cellulose, two candidate proteins from sonicated supernatant from HP were identified. Several partial amino acid sequences of the peptides derived from affinity-purified proteins were obtained By searching homologous sequences in the genome data of HP, one was identified as heat shock protein 60 (HSP) and the other as a functionally unknown protein. Since other researchers hypothesized HSP as a putative adhesin acting at the initial step of bacterial attachment, we cloned HSP gene to clarify the binding specificity of HSP. This work is now in progress. Secondary, we tried to characterize the adhesion receptors in Mongolian gerbils which have been known as a suitable animal model of human gastric ulcer and cancer induced by HP infection. In this animal, sulfatides were abundantly expressed in the gastric mucosa compared with mice, indicating the higher number of bacterial attachment seen in this animal may be due to receptor abundance. This result is now submitted for publication. To further confirm the role of sulfatide as a receptor, we have cloned human sulfotransferase. The expression of sulfotransferase in the sulfatide-deficient cells is now in progress.

幽门螺杆菌（HP）附着于胃上皮是使感染永久化的关键步骤。机体与上皮的紧密粘附深刻影响上皮功能，引起多种疾病。这种附着是由一种特殊的细菌蛋白质介导的，这种蛋白质被称为粘附素，它能识别特定的受体。在大多数情况下，细胞表面糖缀合物已被证明是细菌粘附受体。在HP的情况下，已经报道了几种具有不同受体特异性的推定粘附素。在这个项目中，我们试图识别特异性识别硫fatide的粘附素。采用两种不同的亲和层析，一种是肝素-sepharose层析，另一种是硫酸纤维素层析，从HP超声上清中鉴定了两种候选蛋白。通过在HP基因组数据中搜索同源序列，获得了亲和纯化蛋白衍生的多肽的部分氨基酸序列，其中一个为热休克蛋白60 (HSP)，另一个为功能未知蛋白。由于其他研究者假设HSP是一种假定的粘附素，在细菌附着的初始阶段起作用，我们克隆了HSP基因来阐明HSP的结合特异性。这项工作目前正在进行中。其次，我们试图表征蒙古沙鼠的粘附受体，蒙古沙鼠被认为是HP感染引起的人类胃溃疡和癌症的合适动物模型。在该动物中，与小鼠相比，硫脂脂在胃粘膜中大量表达，表明该动物中细菌附着数量较高可能是由于受体丰富所致。这个结果现在提交发表。为了进一步确认硫脂作为受体的作用，我们克隆了人硫转移酶。巯基转移酶在硫脂缺乏细胞中的表达正在进行中。