Switching at the cellular level in the white-opaque transition of Candida albicans

Abstract

The 'white-opaque transition' in Candida albicans strain WO-1 provides a unique system for analysing high-frequency switching at the cellular level because of the difference in the budding phenotypes of the white and opaque phases. Single white and opaque cells were placed on agar and monitored for the dynamics of cell division, microcolony genesis and switching to the alternative phase. It is demonstrated that at 24 degrees C, opaque cells can switch directly to white cells but white cells first generate an elongate, pseudohyphal-shaped precursor in the transition to an opaque cell. Cells in either phase can generate a daughter cell in the alternative phase, then revert immediately to the genesis of subsequent daughter cells in the original phase. By developing a mathematical model for switching at the cellular level which subtracts mother cells and switched daughter cells from the pool of switching candidates, the probability for an opaque cell to generate a white daughter cell in any single generation was calculated to be 1.0 x 10(-1) and the probability for a white cell to generate an opaque daughter cell in any single generation was calculated to be 1.7 x 10(-5) at 24 degrees C on nutrient agar. The mean number of generations before an opaque cell generated a white daughter cell was calculated to be 3.4 and the mean number before a white cell formed an opaque cell was calculated to be 15.8 at 24 degrees C on nutrient agar. Finally, high-temperature induction of the opaque to white transition was analysed at the cellular level and demonstrated to involve frequent bipolar formation of white daughter cells on the original opaque mother cell, and in some cases intermediate phenotypes.