FUNCTIONAL SCREENING FOR CANDIDA ALBICANS VIRULENCE GPI-PROTEINS

Lundquist Institute For Biomedical Innovation At Harbor-Ucla Medical Center, Torrance CA

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Abstract

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. Candidiasis is a life-threatening infection that occurs in patients whose immune systems are not working properly. Candida albicans is the leading cause of Candida infections originating from the blood stream. Despite antifungal therapy, mortality resulting from these infections due to C. albicans remains unacceptably high and continues to increase. In light of these concerns, it is critical that mechanisms by which C. albicans initiate the infection in the blood stream be identified. C. albicans must bind to and traverse the vascular endothelium (cells that line the blood vessels) to escape from the blood vessel and infect a target organ such as kidneys. Therefore, a critical step in crossing the endothelial barrier involves adherence to and invasion of vascular endothelial cells by C. albicans. Additionally, during these processes C. albicans must evade killing by circulating white blood cells. To perform these experiments, it is necessary to grow in the test tube the same type of human cells that the fungus normally interacts with while in the blood stream (i.e. human endothelial cells and white blood cells). The most available, richest source of endothelial cells is the umbilical cord veins. The umbilical cords are anonymously removed from placentas that are to be discarded after delivery. White blood cells (neutrophils) will be harvested from healthy volunteers after signing an informed consent.