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

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。前言：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。口腔和食管念珠菌病在艾滋病毒/艾滋病患者中特别常见。这种疾病的复发性需要长期使用抗真菌药物治疗，这可能是导致耐药菌株出现的一种策略。C.白色念珠菌在酵母和菌丝生长形式之间转换的能力对于发病机理是必不可少的。转变为丝状生长伴随着真菌液泡的扩张，产生空的细胞隔室。 目的：本研究的目的是确定C。白色念珠菌，并建立其在口腔组织的入侵的重要性。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进行拟议的研究。2.获得运营高效且成功的实验室所需的技能。3.最终获得R 01级的NIH资助。 研究方法：来自成功获得NIH资助的经验丰富的研究人员的结构化指导;参与COBRE计划提供的教育活动;利用COBRE设备和行政设施。 结果如下：以前，我们构建了空泡生物发生缺陷的突变体，这些突变体不能形成细丝，并且在杀死巨噬细胞系方面存在缺陷。自从加入COBRE计划以来，PI在一次关于疟疾的国际会议上以及在路易斯安那州立大学的一次工作进展研讨会上介绍了这一数据。实验工作已经开始，这将包括参与空泡化的细胞组分的表达和定位分析，参与空泡扩张的膜运输途径/组分的鉴定，以及确定突变株是否在口腔上皮组织的侵袭中有缺陷。 结论：本研究为阐明C.白色念珠菌从良性真菌转变为侵袭性病原体。COBRE计划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.