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 degrees 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 degrees 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.