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.
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