Characterization of Candida albicans microtubules

描述 白色念珠菌是一种条件致病菌，可引起阴道，口腔和肺部 免疫功能低下个体的感染和 获得性免疫缺陷患者。C.白色念珠菌感染 由于C.白色念珠菌细胞和 人体细胞然而，哺乳动物和念珠菌属细胞中的有丝分裂纺锤体是 构造不同。此外，在这些方面也存在显著差异。 真菌和哺乳动物微管蛋白的序列，它们是构建单元 有丝分裂纺锤体在生物化学和 关于念珠菌微管蛋白的功能水平，几乎一无所知 关于念珠菌微管的聚合和动力学性质。 这个想法是，了解真菌细胞微管蛋白之间的差异， 和哺乳动物微管蛋白可能导致开发新的和选择性的药物， 真菌疾病的治疗因此，建议开发一个 大规模纯化C. Albicans微管蛋白基于先前的 在这个实验室中成功地从酿酒酵母微管蛋白。的 微管蛋白的特点是生化，聚合和动态 确定念珠菌微管的性质。最后， 两种已知微管靶向抗真菌药物（苯菌灵和 灰黄霉素）与念珠菌微管蛋白将被确定和机制， 其中药物调节聚合和动力学性质， 将阐明微管蛋白。

DESCRIPTION Candida albicans, an opportunistic pathogen, can cause vaginal, oral and lung infections in immunocompromised individuals and systemic tissue damages in acquired immunodeficiency patients. The chemotherapy of C. albicans infections is limited because of the strong similarities between C. albicans cells and human cells. However, the mitotic spindles in mammalian and Candida cells are constructed differently. In addition, significant differences exist in the sequences of fungal and mammalian tubulins, which are the building block units of mitotic spindles. Little information is available at biochemical and functional levels about Candida tubulin, and virtually nothing is known regarding the polymerization and dynamics properties of Candida microtubules. The thinking is that understanding the differences between fungal cell tubulin and mammalian tubulin could lead to development of new and selective drugs for the treatment of fungal diseases. Therefore, it is proposed to develop a large-scale purification strategy for C. Albicans tubulin based upon previous success in this laboratory with tubulin from Saccharomyces cerevisiae. The tubulin will be characterized biochemically, and the polymerization and dynamic properties of Candida microtubules determined. Finally, the mechanism of interaction of two known microtubule-targeted antifungal drugs (benomyl and griseofulvin) with the Candida tubulin will be determined and the mechanisms by which the drugs modulate the polymerization and dynamics properties of the tubulin will be elucidated.