Mechanisms of aggregation accompanying morphogenesis in Candida albicans

Cultures of Candida albicans yeast cells do not normally aggregate, but extensive aggregation accompanies the induction of mycelial growth, indicating the occurrence of cell surface changes during the yeast to mycelial transition. Aggregation correlated with the formation of germ tubes as did changes in surface charge determined by attachment to ion exchange sepharose beads. Yeast cells of all strains examined were negatively charged and attachment to positively charged (DEAE) sepharose beads increased following germ tube formation. If Mg2+ was present during germ tube formation, a high degree of clumping occurred that could only be dispersed by treatment with protein-disrupting agents. Trypsin, chymotrypsin, SDS, urea, guanidine HCl and dithiothreitol but not EDTA or EGTA caused irreversible dispersal of aggregates, although germ tube aggregates dispersed by treatment with buffers at high pH reaggregated if neutralized or if calcium ions were added. Germ tube cultures produced in divalent cation-deprived medium formed aggregates that were readily dispersed by washing. However, the addition of Mg2+ or other divalent cations (Ca2+, Zn2+, Cu2+, Fe2+) caused immediate aggregation of these cultures. These results suggest that divalent cation crossbridging between opposing anionic sites and protein interactions act synergistically to promote aggregation of C. albicans germ tube cells.