Kate J. Graham

Using Chemical Ecology to Locate New Antifungal Natural Products

Abstract The quest for new antifungal drugs is critical for several reasons. Immune suppression causes susceptibility to fungal infections. The number of immune-suppressed individuals continues to rise as society is faced with an aging population, an increase in AIDS infected patients, and medical advances. Most drugs used to treat mycological infections have low bioavailability or are too toxic for prolonged use. Also, many new fungal strains are emerging with drug resistance as fungal pathogens are exposed to extended pharmaceutical treatment. As the need for new antifungal drugs continues to rise, chemical ecology appears to be an attractive tool for identification of such compounds. In competitive ecosystems, it is generally accepted that many organisms thrive because they produce secondary metabolites providing a selective advantage over competing organisms. Biorational criteria, in this context, means using the ecology of natural systems to reveal organic chemicals with specific bioactivities. By employing biorational criteria in selecting sources, potential drugs can be more effectively located. Therefore, biorationale predicts organisms encountering fungal competitors or pathogens will be a good source of fungistatic or fungicidal chemicals. Ecological clues point to a variety of sources which are expected to produce fungistatic secondary metabolites. Examples of such sources include antagonistic fungi, plants with fungal pathogens, and mycoparasites. Studies of antagonistic species can provide useful information for scientists interested in chemical ecology, but can also serve as a valuable complement to random, high-throughput screening for new bioactive compounds.