Candida albicans is one of the most important opportunistic pathogenic fungi. Weakening of the defense mechanisms of the host, and the ability of the

• Glucans are the most abundant compounds in the fungal cell walls. • The most common type of glucose bonding is 1 → 3, both alpha and beta. • Microfibrillar glucans with chitin provide rigidity to the fungal wall. • Fungal beta glucans act as PAMPS during infection of animals and plants.

The fungal cell wall is a coherent structure formed by microfibrillar polysaccharides and amorphous material made of other polysaccharides and protei

Human mycoses have become a threat to health world-wide. Unfortunately there are only a limited number of antimycotic drugs in use. Promising targets for drugs specific against fungi are those affecting chitin synthesis. Chitin is absent in vertebrates, and is essential for fungal wall integrity. A thorough knowledge of the mechanism of chitin synthesis is required to design specific inhibitors. We review here our current understanding of the process, and the most promising drugs that inhibit it. Chitin is made by chitin synthases requiring specific microvesicles, the chitosomes, for intracellular transport. Fungi contain several chitin synthases, some of which may be essential at a certain stage. This phenomenon is important to take into account for drug design. The most widely studied chitin synthase inhibitors are polyoxins and nikkomycins that probably bind to the catalytic site of chitin synthases. These are not equally susceptible to the drugs. In Saccharomyces cerevisiae the order of sensitivity is: Chs3p > Chs1p > Chs2p. Main problems for their succesful use in vivo are: low permeability, and different susceptibility of fungal species, and variable responses in animal models. Chemical modifications have been proposed to make more potent derivatives. Other synthetic or natural compounds are also promising as possible inhibitors, but their properties are less well known. Rational drug design has proceeded only on the basis of existing inhibitors, because the structure of the active site of chitin synthase is unknown. Undoubtedly, determination of this, and the biosynthetic mechanism will reveal unexpected drug targets in the future.