NOVEL NEW ENZYME & PRODUCT FROM ENCYSTING GIARDIA

贾第鞭毛虫（Giardia pestilalis）（syn. G. lamblia，G.（图）A 病原性原生动物寄生虫，在世界范围内是导致 在水中爆发的肠道疾病，托儿所或日托 设施和同性恋者 疾病的粪口传播 当活的包囊被摄入时发生， 小肠上部出现两个滋养体。 滋养体定植在小肠中，至少部分在 在胆汁的刺激下，它们形成新的囊肿（包囊）， 粪便 在包囊形成过程中，贾第虫滋养体合成一种 丝状孢囊壁，大部分由 N-乙酰半乳糖胺（GaINAc），这是检测不到的，在 非包囊滋养体。 为了实现这一目标，贾第虫 滋养体使用诱导酶的合成途径来转化 内源性葡萄糖转化为GaINAc。 这条道路不仅是至关重要的， 它们的细胞分化从滋养体到包囊，但代表了一个 对贾第虫的潜在化疗攻击点。 之甚少 已知的酶的调节或遗传控制， 包括贾第虫中的诱导型GaINAc合成途径，也不包括 以前未描述的酶活性，暂时称为 “囊壁合成酶”，它似乎将GaINAc固定到不溶性的 构成贾第鞭毛虫外部囊壁的细丝。 当前 该项目继续通过1）纯化来研究该途径， 表征和定位可诱导的颗粒状“囊壁 合成酶”;和2）确定其化学性质 未经鉴定的产品，这可能是一个主要组成部分 贾第虫囊壁 此处生成的详细信息将 提供了重要的信息，关于一个关键的代谢途径至关重要， 贾第虫包囊和传播（也许在其他 产包囊的原生动物）。 目前有几种药物被用于 治疗贾第虫病，许多有不愉快的副作用。 有些人， 包括最常用的药物甲硝唑， 变得过时。 虽然对甲硝唑的耐药性还没有 在实践中成为一个问题，体内和体外抗性已经被 这是一个潜在的问题，因此存在一个潜在的问题。

Giardia duodenalis (syn. G. lamblia, G. intestinahs) is a pathogenic protozoan parasite, and worldwide is a leading cause of intestinal disease in waterbome outbreaks, nursery or day-care facilities, and homosexuals. Fecal-oral transmission of the disease occurs when viable cysts are ingested, and excystation occurs in the upper small intestine with the emergence of two trophozoites. Trophozoites colonize the small intestine where, at least in part stimulated by bile, they form new cysts (encystment) which are shed in the feces. During encystment, Giardia trophozoites synthesize a filamentous cyst wall that is composed, in large part, of N-acetylgalactosarnine (GaINAc), which is undetectable in non-encysting trophozoites. In order to accomplish this, Giardia trophozoites use a synthetic pathway of inducible enzymes to convert endogenous glucose to GaINAc. This pathway is not only paramount in their cytodifferentiation from trophozoite to cyst, but represents a potential point of chemotherapeutic attack against Giardia. Little is known of the regulation or genetic control of the enzymes that comprise the inducible GaINAc synthetic pathway in Giardia, nor of a previously undescribed enzyme activity, tentatively referred to as "cyst wall synthetase", which appears to fix GaINAc into the insoluble filaments that compose the outer cyst wall of Giardia. The current project continues studying this pathway by 1) purifying, characterizing and localizing the inducible, particulate "cyst wall synthetase"; and 2) determining the chemical nature of its uncharacterized product, which is likely to be a major component of the Giardia cyst wall. The detailed information generated here will provide important information about a key metabolic pathway vital to Giardia encystment and transmission (and perhaps in other cyst-producing protozoa). Several drugs are currently being used to treat giardiasis and many have unpleasant side effects. Some, including the most frequently used drug, metronidazole, are at risk of becoming obsolete. While resistance to metronidazole has not yet become a problem in practice, in vivo and in vitro resistance has been demonstrated and thus a potential problem exists.