Chs1 of Candida albicans is an essential chitin synthase required for synthesis of the septum and for cell integrity

CaCHS1 of the fungal pathogen Candida albicans encodes an essential chitin synthase that is required for septum formation, viability, cell shape and i ntegrity. The CaCHS1 gene was inactivated by first disrupting one allele us ing the ura-blaster protocol, then placing the remaining allele under the c ontrol of the maltose-inducible, glucose-repressible MRP1 promoter. Under r epressing conditions, yeast cell growth continued temporarily, but daughter buds failed to detach from parents, resulting in septumless chains of cell s with constrictions defining contiguous compartments. After several genera tions, a proportion of the distal compartments lysed. The conditional Delta chs1 mutant also failed to form primary septa in hyphae; after several gen erations, growth stopped, and hyphae developed swollen balloon-like feature s or lysed at one of a number of sites including the hyphal apex and other locations that would not normally be associated with septum formation. CHS1 therefore synthesizes the septum of both yeast and hyphae and also maintai ns the integrity of the lateral cell wall. The conditional mutant was aviru lent under repressing conditions in an experimental model of systemic infec tion. Because this gene is essential in vitro and in vivo and is not presen t in humans, it represents an attractive target for the development of anti fungal compounds.