Identification and characterisation of molecules involved in the pathogenicity of Entamoeba histolytica

溶组织内阿米巴致病性相关分子的鉴定和表征

基本信息

批准号：
98301232
负责人：
Professorin Dr. Iris Bruchhaus
金额：
--
依托单位：
Bernhard-Nocht-Institut für Tropenmedizin (BNITM)
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2009
资助国家：
德国
起止时间：
2008-12-31 至 2014-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/98301232?language=en
关键词：
Identification characterisation molecules involved pathogenicity

项目摘要

Entamoeba histolytica is known for it´s extraordinary capacity to efficiently destroy human tissues, leading to invasive diseases such as ulcerative colitis or extraintestinal abscesses. Various molecules have been considered important for amoeba pathogenicity. However, all these activities are present in pathogenic as well as in non-pathogenic amoeba isolates, calling into question the importance of these molecules for E. histolytica pathogenicity. We recently identified two syngenic clones (A and B) derived from the widely used laboratory E. histolytica strain HM-1:IMSS, which consistently differ in virulence. Clone A is incapable to induce liver abscesses when injected into rodents, whereas a relatively small number of cells from clone B are able to provoke large abscesses. The major goal of this study is to identify molecules that are responsible for the pathogenicity of E. histolytica. Therefore, a tripartite strategy is chosen that comprises: (i) DNA-microarray and proteome analysis of the two E. histolytica clones, (ii) functional analysis of candidate genes using transgenic amoebae, (iii) focussing on an interesting new family of genes that include numerous differentially expressed candidate genes already identified. The combination of molecular and biochemical studies using the two different amoeba clones as well as the introduction of transgenic amoebae may allow to unravel the molecular basis that determines E. histolytica pathogenicity.

Entamoeba Hissolytica以有效破坏人体组织的非凡能力而闻名，导致侵入性疾病，例如溃疡性结肠炎或胸腔外脓肿。各种分子被认为对变形虫致病性很重要。但是，所有这些活性都存在于致病性和非致病变形虫分离株中，这使这些分子质疑这些分子对溶组织溶液性大肠杆菌的致病性的重要性。我们最近确定了两个源自广泛使用的实验室E. issolytica菌株HM-1：IMS的合成克隆（A和B），它们在病毒上持续不同。当注入啮齿动物时，克隆A无法诱导肝脓肿，而克隆B的相对较少的细胞能够引起大型脓肿。这项研究的主要目的是鉴定造成病原体致病性的分子。因此，选择三方策略是：（i）使用转基因变形虫（III），（iii）重点关注一个有趣的新基因家族，其中包括许多不同表达的候选基因，对候选基因进行了DNA微阵列和蛋白质组分析，（III）候选基因的功能分析。使用两个不同的变形虫克隆以及转基因变形虫的引入的分子和生化研究的组合可能允许揭示决定组织溶血性大肠杆菌致病性的分子基础。