EFFECTS OF BLEOMYCIN ON AIDS ASSOCIATED CANDIDA ALBICANS: CELL WALL STRUCT

真菌感染是临床管理中的一个严重问题。 爱滋病患者。如果不针对病原真菌进行治疗， 它们通常对艾滋病患者是致命的。的长期目标 本项目是为了确定和理解生物多样性的基本机制 博莱霉素的细胞壁效应在艾滋病机会主义中的作用 真菌病原体，白色念珠菌。具体目标是确定 细胞壁的某些细胞、分子和生化基础 博莱霉素对白色念珠菌的影响，并测定其哪些成分 白色念珠菌的细胞壁与博莱霉素反应。使用多个 实验方法，我们将确定范围 白念珠菌分离株对杀戮、细胞壁破坏、 和博莱霉素治疗引起的染色体断裂，并确定 博莱霉素处理引起的细胞壁的特异性变化 利用透射电子显微镜，对细胞进行生化研究 壁组分和脉冲场凝胶电泳法测定 DNA断裂和电泳法核型分析。这项研究是设计的 博莱霉素抗真菌作用的基本机制研究 在白色念珠菌细胞壁上。这些基本信息应该会导致 了解白色念珠菌分离株的基本生物学和 小剂量博莱霉素或类似物的治疗作用 用于急性治疗的抗真菌药物。低剂量的药物或类似物 可以作为单一药物或一种或多种药物使用 联合用药，特别是当白色念珠菌对 另一种抗真菌药物。这项研究的信息应该是 也导致识别潜在的靶标结构 其他抗真菌药物，并协助抗真菌药物的设计和 针对关键结构的治疗。

Fungal infections are a serious problem in the clinical management of AIDS patients. Without treatment targeted to the pathogenic fungi, they are often fatal to AIDS patients. The long term objectives of this project are to determine and understand the basic mechanism of action of the cell wall effects of bleomycin on the AIDS opportunistic fungal pathogen, Candida albicans. The specific aims are to determine some of the cellular, molecular and biochemical bases for cell wall effects of bleomycin in C. albicans, and determine which components of the C. albicans cell wall react wit bleomycin. Using several experimental approaches, we will determine the range of susceptibilities of C. albicans isolates to killing, cell wall damage, and chromosomal breaks caused by bleomycin treatments, and determine specific changes in the cell wall associated with bleomycin treatments using transmission electron microscopy, biochemical studies of cell wall components, and pulsed-field gel electrophoresis for assays of dna breaks and electrophoretic karyotyping. The research is designed to determine the basic mechanism of the antifungal action f bleomycin on C. albicans cell walls. This basic information should lead to an understanding of the basic biology of C. albicans isolates and therapeutic usefulness of low doses of bleomycin or an analog as an antifungal for acute treatments. Low doses of the drug or an analog may be able to be used as a single agent or in one or more drug combinations, particularly when C. albicans develops resistance to another antifungal drug. The information from this research should also lead to the identification of potential target structures for additional antifungal drugs and assist in antifungal drug design and therapy to target critical structures.