Pathways regulating amoebic cyst formation

描述（由申请人提供）：溶组织内阿米巴感染约1%的世界人口，每年造成多达10万人死亡。寄生虫的致病滋养体阶段在宿主结肠内分化为感染性囊肿形式，诱导这种分化的刺激因素直到现在才变得清楚。我们之前已经发现，半乳糖末端分子，包括结肠粘液中的分子，在囊肿形成之前被滋养体用来形成细胞聚集体。我们现在发现，由常驻结肠细菌群体产生的短链脂肪酸可以以浓度依赖的方式调节内阿米巴囊肿的形成过程。短链脂肪酸对寄生虫的作用不同于这些化合物对宿主其他细胞的作用，但它们可能通过相似的分子机制起作用。该项目将研究这些化合物调节囊肿形成的机制，并将确定这些化合物对寄生虫中基因和蛋白质表达的影响程度。

DESCRIPTION (provided by the applicant): Entamoeba histolytica infects approximately 1% of the world's population, and causes up to 100,000 deaths annually. The disease-causing trophozoite stage of the parasite differentiates into the infectious cyst form while within the host colon, and the stimuli that induce this differentiation are only now becoming clear. We had previously found that galactose-terminated molecules, including those in colonic mucus, are used by the trophozoites to form cellular aggregates just prior to cyst formation. We have now found that short chain fatty acids, which are produced by the resident colonic bacterial population, can regulate the Entamoeba cyst formation process in a concentration-dependent manner. The effects of short chain fatty acids on the parasites are different from the effects these compounds have on other cells of the host, but they may be working through similar molecular mechanisms. This project will examine the mechanism(s) whereby these compounds regulate cyst formation, and will determine the extent of the effects these compounds have on gene and protein expression in the parasite.