Scientists from Howard Hughes Medical Institute in Ann Arbor, Michigan have made a discovery that may help us win the biomedical war against fungal pathogens. As published in Genes & Development, Dr. Martin Schrder and colleagues have uncovered a specific biological program which prevents the development of the pathogenic form of several fungi, and have thus paved the way for the design of new anti-fungal agents. Depending upon nutrient availability, many fungi are able to switch between two different morphological forms: a unicellular yeast form and a multicellular filament form. For a number of medically and agriculturally relevant fungi, the filament form is necessary for pathogenicity.
Ustilago maydis, Cryptococcus neoformans, and Candida albicans may not sound familiar, but the effects of these fungi certainly are. Well known to any farmer, Ustilago maydis is the cause of corn smut disease. Cryptococcus neoformans is responsible for meningitis. Candida albicans, the most prevalent yeast species in the human GI tract, causes vaginal yeast infections, oral thrush, and can invade tissues and produces fatal systemic infections in immunocompromised people. Under nitrogen-poor conditions, each of these fungi switch to filament form and thus become pathogenic. This physiological response to nutrient availability has been well documented. It is only now beginning to be understood.
Schrder and colleagues have discovered that the unfolded protein response (UPR) mediates this morphological response. The UPR is a cellular stress response, conserved from yeast to humans. Normally, proteins are folded into their proper conformations in the endoplasmic reticulum (ER) compartment of a cell. When unfolded or misfolded proteins accumulate in the ER, the UPR is activated to transiently decrease the level of protein production and ensure that proper folding occurs. Schrder and colleagues have demonstrated that an active UPR represses filament formation. Their experi
'"/>
Contact: Nora Poppito
poppito@cshl.org
Cold Spring Harbor Laboratory
30-Nov-2000