CO₂ Regulates White-to-Opaque Switching in Candida albicans

To mate, Candida albicans must undergo homozygosis at the mating type-like locus MTL [1, 2], then switch from the white to opaque phenotype [3, 4]. Paradoxically, when opaque cells are transferred in vitro to 37°C, the temperature of their animal host, they switch en masse to white [5-7], suggesting that their major niche might not be conducive to mating. It has been suggested that pheromones secreted by opaque cells of opposite mating type [8] or the hypoxic condition of host niches [9, 10] stabilize opaque cells. There is, however, an additional possibility, namely that CO₂, which achieves levels in the host 100 times higher than in air [11-13], stabilizes the opaque phenotype. CO₂ has been demonstrated to regulate the bud-hypha transition in C. albicans [14, 15], expression of virulence genes in bacteria [16], and mating events in Cryptococcus neoformans [14, 17]. We tested the possibility that CO₂ stabilizes the opaque phenotype, and found that physiological levels of CO₂ induce white-to-opaque switching and stabilize the opaque phenotype at 37°C. It exerts this control equally under anaerobic and aerobic conditions. These results suggest that the high levels of CO₂ in the host induce and stabilize the opaque phenotype, thus facilitating mating.