Overview
Every year worldwide, millions of people experience morbidity and mortality as a consequence of severe fungal disease. In the United States, mortality from invasive fungal disease is approximately 50 percent. People with AIDS, chemotherapy patients, and transplant recipients are at highest risk of developing life-threatening infections, but many fungi also cause disease in apparently healthy individuals. The environmental yeast Cryptococcus epitomizes this trend. Like many fungi, infection with Cryptococcus occurs when it is inhaled into the lung from which it can disseminate to the central nervous system (CNS) and cause disease. In the CNS Cryptococcus causes fungal meningoencephalitis that is uniformly fatal without treatment and fatal ~25 percent of the time with the best treatments we have to offer. This high incidence of mortality is consistent with other invasive fungal diseases and indicative of the dire need for improved therapeutic agents. Current antifungal therapeutics are relatively limited because of high toxicity or insufficient efficacy, because those compounds that interfere with fungal biology or are toxic to fungi, tend also to interfere with or be toxic to humans and animals. While vegetative fungi are similar metabolically and biochemically to plant and animal cells, fungi also sporulate and germinate. Thus, chemical inhibitors of fungal germination are potentially highly useful compounds in antifungal compositions.
;
