ROLE OF VACUOLE EXPANSION IN THE ORAL PATHOGEN CANDIDA ALBICANS: HIV

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。在免疫功能低下的患者体内，白色念珠菌可侵入粘膜组织引起多种疾病。口腔和食道念珠菌病在艾滋病毒/艾滋病患者中尤为常见。这种疾病的复发性需要用抗真菌药物进行长期治疗，这一策略可能导致耐药分离株的出现。白色念珠菌在酵母菌和菌丝生长形式之间切换的能力对发病至关重要。向丝状生长的转变伴随着真菌液泡的扩张，产生“空”的细胞区室。目的：本研究的目的是明确白色念珠菌利用这种新的分化程序背后的机制，并确定其在口腔组织侵袭中的重要性。COBRE方案提供的资源将用于：1。建立一个实验室，配备必要的设备和人员进行拟议的研究。2. 获得运行一个富有成效和成功的实验室所需的技能。3. 最终获得R01水平的NIH资助。方法：由成功获得NIH资助的经验丰富的研究人员进行结构化指导；参加COBRE项目提供的教育活动；COBRE设备和行政设施的使用情况。结果：先前我们构建了液泡生物发生缺陷的突变体，这些突变体不能成丝，也不能杀死巨噬细胞。自从加入COBRE项目以来，P.I.在一个关于念珠菌病的国际会议上，以及在路易斯安那州立大学的一个正在进行的研讨会上，展示了这些数据。实验工作已经启动，包括液泡形成过程中细胞成分的表达和定位分析，液泡扩张过程中膜运输途径/成分的鉴定，以及确定突变菌株在口腔上皮组织的侵袭中是否存在缺陷。结论：本研究有助于明确白色念珠菌由良性共生菌向侵袭性病原菌转变的基本机制。COBRE计划将使初级调查员发展必要的技能，成为一名成功的独立调查员。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Introduction: Within the immunocompromised patient Candida albicans can invade mucosal tissue to cause a variety of disease. Oral and esophageal candidiasis are particularly common among HIV/AIDS patients. The recurrent nature of this disease necessitates long term treatment with antifungals, a strategy which may have contributed to the emergence of drug resistant isolates. C. albicans ability to switch between yeast and hyphal growth forms is essential for pathogenesis. The switch to filamentous growth is accompanied by expansion of the fungal vacuole, to produce ¿empty¿ cell compartments. Objective: The goal of this research is to define the mechanism behind this novel differentiation program utilized by C. albicans, and establish its importance during invasion of oral tissue. The resources provided under the COBRE program will be utilized to: 1. Set up a lab with the necessary equipment and personnel to conduct the proposed research. 2. Acquire skills needed to run a productive and successful laboratory. 3. Ultimately obtain NIH funding at the R01 level. Methods: Structured mentoring from experienced researchers who have successfully obtained NIH funding; participation in educational activities provided by the COBRE program; utilization of COBRE equipment and administrative facilities. Results: Previously we constructed mutants defective in vacuole biogenesis, which were unable to filament and deficient in the killing of a macrophage cell line. Since joining the COBRE program, the P.I. has presented this data at an international conference on Candidiasis, and at a work in progress seminar at LSU. Experimental work has been initiated which will include expression and localization analysis of cellular components involved in vacuolation, identification of the membrane trafficking pathways/components involved in vacuole expansion, and determining if the mutant strains are defective in the invasion of oral epithelial tissue. Conclusion: The proposed research will help define the fundamental mechanisms underlying C. albicans switch from benign commensal to invasive pathogen. The COBRE program will enable the junior investigator to develop the necessary skills to become a successful independent investigator.