The “Finger,” a Unique Multicellular Morphology of Candida albicans Induced by CO 2 and Dependent upon the Ras1-Cyclic AMP Pathway

Abstract

ABSTRACT Most experiments exploring the basic biology of pathogenic microbes are performed in vitro under conditions that do not usually mimic those of their host niche. Hence, developmental programs initiated by specific host cues may be missed in vitro . We have tested the effects of growing low-density agar cultures of the yeast pathogen Candida albicans in concentrations of CO 2 found in the gastrointestinal tract. It is demonstrated that in physiological concentrations of CO 2 at 37°C, yeast cells form a heretofore undescribed multicellular “finger” morphology distinct from a previously described stalk-like structure induced by high doses of UV irradiation that kills more than 99.99% of cells. The finger extends aerially, is uniform in diameter, and is visible to the naked eye, attaining lengths of 3 mm. It is composed of a basal yeast cell monolayer adhering to a semispherical crater formed in the agar and connected to a basal bulb of yeast cells at a fragile interface. The bulb extends into the long shaft. We propose that a single, centrally located hypha extending the length of the shaft forms buds at compartment junctions that serve as the source of the yeast cells in the shaft. A mutational analysis reveals finger formation is dependent upon the pathway Ras1→Cdc35→cyclic AMP (cAMP) (PDE2—|)→Tpk2→Tec1. Because of the mechanically fragile interface and the compactness of bulb and shaft, we suggest that the finger may function as a multicellular dispersal mechanism produced in host niches containing high levels of CO 2 .