Supplements to Support Candida DNA Microarray Facilities

描述(改编自调查者摘要)：发生 由于抗生素的增加，口咽部念珠菌病急剧上升 免疫系统受损个体的使用率和更长的存活期 包括癌症化疗患者、糖尿病患者、艾滋病患者和 早产儿。可用于临床的抗真菌药物相对较少 口腔或全身念珠菌病的治疗。更多地使用这些代理来 治疗晚期艾滋病和癌症患者的念珠菌病已经导致 出现具有抗真菌耐药性的念珠菌种类，特别是对 以唑类为基础的药物。组蛋白(HSTS)是由 人类的主要唾液腺。在体外，HST-5是最有效的念珠菌杀伤剂 能杀死90%到100%的念珠菌的家族的成员 生理浓度。HSTS的有效抗真菌活性，缺乏 对人类的毒性和杀灭耐唑酵母菌株的能力 详细了解他们的行动机制的重要性。 HSTS杀灭念珠菌功能的改进及口腔HST的发展 传递系统还需要关于HST诱导的级联反应的信息 导致白念珠菌死亡的细胞事件。先前的研究表明，HST 其作用机制不同于其他特指的抗真菌药物 这种致死效应的诱导是通过三磷酸腺苷启动的一种新途径 白念珠菌细胞外流，发生在细胞膜完好的情况下。 建议进行研究以检查HST诱导的ATP释放的相关特性， 它在HST诱导的ATP释放导致细胞死亡后的细胞效应， HST细胞内转运杀灭念珠菌活性的要求 研究cAMP、ABC转运体和嘌呤能的潜在参与 白色念珠菌中的受体对HST 5的反应。这些研究将有助于 HST产生酵母的新型胞内途径的特性 细胞死亡，并导致进一步了解ATP外流作为一种 细胞调节或信号传递过程。

DESCRIPTION (adapted from the Investigator's abstract): Incidence of oropharyngeal candidiasis has risen dramatically due to increased antibiotic usage and longer survival of individuals with compromised immune systems including patients on cancer chemotherapy, diabetics, AIDS patients and premature infants. Relatively few antifungal drugs are available for clinical treatment of oral or systemic candidiasis. Increased use of these agents to treat candidiasis in late stage AIDS and cancer patients has resulted in emergence of Candidal species with antifungal drug resistance, especially to azole-based drugs. Histatins (Hsts) are small cationic polypeptides produced by human major salivary glands. In vitro, Hst 5 is the most potent candidacidal member of the family which kills 90% to 100% of Candida species at physiological concentrations. Hsts' potent antifungal activity, lack of toxicity to humans and ability to kill azole-resistant yeast strains underscore the importance of detailed understanding of their mechanism of action. Improvements in candidacidal function of Hsts and development of oral Hst delivery systems also require information about the Hst-induced cascade of cellular events leading to C. albicans death. Previous studies showed that Hst mechanism of action is unique from other characterized antimycotic drugs in that induction of lethal effect is through a novel pathway initiated by ATP efflux from C. albicans cells, which occurs while the cell membrane is intact. Studies are proposed to examine related properties of Hst-induced ATP release, its cellular effects following Hst-induced ATP release leading to cell death, requirements for intracellular transport of Hst for candidacidal activity and examine potential involvement of cAMP, ABC transporters and purinergic receptors in C. albicans response to Hst 5. These studies will contribute to characterization of novel intracellular pathways utilized by Hst to cause yeast cell death and lead to further understanding of the role of ATP efflux as a cell regulatory or signaling process.