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Cell
Wall Biogensis
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Fungal infections are a frequent and growing cause of morbidity
and mortality in the ever-increasing organ transplant, cancer,
and HIV/AIDS patient populations. In recent years, antifungal
drugs that target the enzymes responsible for the synthesis of
cell wall components have been developed and are beginning to
be used to treat fungal disease. In particular, members of the
echinocandin class of antifungal agents are potent inhibitors
of cell wall synthesis in many pathogenic fungi, but display
very low potency against Cryptococcus neoformans, a medically
significant fungal pathogen. Because the inherent echinocandin-resistance
of C. neoformans is likely a direct result of fundamental differences
in the way cell wall biogenesis is regulated in this organism
compared to other fungi, we anticipate that the identification
of key components of signaling and regulatory complexes involved
in cell wall biogenesis will facilitate the elucidation of mechanisms
that promote resistance. To this end, we are working toward the
identification of signaling events involved in cell wall biogenesis
using a variety of biochemical and molecular approaches, including
cell wall composition analysis, yeast two-hybrid library screening,
and two-dimensional gel electrophoresis.
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