Pathways regulating amoebic cyst formation

描述（由申请方提供）：溶组织内阿米巴感染约1%的世界人口，每年导致多达100，000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包囊形式，诱导这种分化的刺激现在才变得清楚。我们以前发现，半乳糖终止的分子，包括结肠粘液中的那些，被滋养体用来在包囊形成之前形成细胞聚集体。我们现在已经发现，由常驻结肠细菌群体产生的短链脂肪酸可以以浓度依赖性方式调节内阿米巴包囊形成过程。短链脂肪酸对寄生虫的影响与这些化合物对宿主其他细胞的影响不同，但它们可能通过类似的分子机制起作用。该项目将研究这些化合物调节包囊形成的机制，并确定这些化合物对寄生虫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.