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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 简介：免疫低下患者体内的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/艾滋病患者中特别常见。这种疾病的复发需要长期使用抗真菌药物治疗，这一策略可能是导致出现耐药菌株的原因之一。白念珠菌在酵母菌和菌丝生长形式之间转换的能力是致病的关键。向丝状生长的转变伴随着真菌液泡的扩张，从而产生空的细胞隔间。 目的：本研究的目的是明确白念珠菌利用这种新的分化程序的机制，并确定其在口腔组织侵袭中的重要性。根据Cobre计划提供的资源将用于：1.建立一个实验室，配备必要的设备和人员来进行拟议的研究。2.掌握运营高效且成功的实验室所需的技能。3.最终获得NIH R01级的资金。 方法：由成功获得NIH资助的有经验的研究人员进行有组织的指导；参与Cobre计划提供的教育活动；使用Cobre设备和行政设施。 结果：以前我们构建了空泡发生缺陷突变体，该突变体不能丝状化，对巨噬细胞系缺乏杀伤作用。自从加入Cobre计划以来，P.I.已经在一次关于念珠菌病的国际会议上和路易斯安那州立大学的工作中研讨会上展示了这一数据。实验工作已经开始，包括参与空泡化的细胞成分的表达和定位分析，涉及空泡扩张的膜运输途径/成分的鉴定，以及确定突变菌株是否在侵袭口腔上皮组织方面存在缺陷。 结论：拟议的研究将有助于确定白色念珠菌从良性共生转变为侵袭性病原体的基本机制。科布雷项目将使初级调查员能够发展成为一名成功的独立调查员所需的技能。

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.