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

溶组织内阿米巴以其非凡的能力而闻名，它能有效地破坏人体组织，导致溃疡性结肠炎或肠外脓肿等侵袭性疾病。各种分子被认为是阿米巴致病的重要因素。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，这使得人们对这些分子对溶组织埃希菌致病性的重要性提出了质疑。我们最近从实验室广泛使用的溶组织乳杆菌HM-1：IMSS菌株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在注射到啮齿动物体内时不能引起肝脓肿，而克隆B的相对少量的细胞能够引起大的脓肿。本研究的主要目的是确定与溶组织性肠杆菌致病相关的分子。因此，我们选择了三方策略，包括：(I)DNA微阵列和蛋白质组分析，(Ii)利用转基因阿米巴对候选基因进行功能分析，(Iii)聚焦于一个有趣的新基因家族，其中包括已确定的大量差异表达的候选基因。利用两个不同的阿米巴克隆进行的分子和生化研究相结合，以及转基因阿米巴的引入，可能会揭开决定溶组织性肠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.