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

溶组织内阿米巴以其有效破坏人体组织的非凡能力而闻名，导致溃疡性结肠炎或肠外脓肿等侵袭性疾病。各种分子被认为对阿米巴原虫的致病性很重要。然而，所有这些活性都存在于致病性和非致病性阿米巴分离物中，这就对这些分子对溶组织芽胞杆菌致病性的重要性提出了质疑。我们最近从广泛使用的实验室溶组织芽胞杆菌菌株HM-1:IMSS中鉴定出两个同源克隆（A和B），它们的毒力一直不同。克隆A注射到啮齿类动物体内后不能诱发肝脓肿，而克隆B的相对少量细胞能够诱发大脓肿。本研究的主要目的是确定负责溶组织芽胞杆菌致病性的分子。因此，我们选择了一个三方合作的策略，包括：(i)对两个溶组织芽孢杆菌克隆进行dna微阵列和蛋白质组分析，（ii）使用转基因变形虫对候选基因进行功能分析，（iii）关注一个有趣的新基因家族，其中包括许多已经确定的差异表达的候选基因。利用这两种不同的阿米巴原虫克隆以及转基因阿米巴原虫的引入，结合分子和生化研究可能会揭示决定溶组织芽胞杆菌致病性的分子基础。

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.