Importance of Chitin Synthesis for Fungal Growth and as a Target for Antifungal Agents

The synthesis of the fungal cell wall component, chitin, has long been considered a possible target for antifungal chemotherapy (for a review see Cassone, 1986), Natural product inhibitors of chitin synthesis, the polyoxins and the nikkomycins, have been found that inhibit the growth of fungi (Bowers et al., 1974; Dahn et al., 1976; Hagenmaier et al., 1979; Isono et al., 1967, 1969). However, both the fact that these agents have not proven to be clinically useful antifungal agents and the low levels of chitin in yeast pathogens have raised questions about the importance of chitin to the fungal cell wall. Recent work on the genetics of chitin synthesis in the ascomycete Saccharomyces cerevisiae indicate that structural genes for chitin synthases may not be required for viability (Baymiller and McCullough, 1990, 1992; Bulawa and Osmond, 1990; Bulawa et al., 1986). To assess the suitability of chitin synthesis as a target for antifungal chemotherapy, this chapter reviews the current understanding of the mode of action of the polyoxins and nikkomycins and the genetics of chitin synthesis in S. cerevisiae that pertain to the question of the requirement for chitin for fungal growth. The evidence obtained from this work strongly supports the view that chitin synthesis is indeed required for S. cerevisiae viability. These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.