Effects of low concentrations of zinc on the growth and dimorphism of Candida albicans: evidence for zinc-resistant and -sensitive pathways for mycelium formation

In this analysis we have examined in detail the effects of low concentrations of zinc on the growth and dimorphism of Candida albicans. Evidence is presented that micromolar concentrations of zinc added to growth cultures grown at 25 degrees C (i) cause a twofold increase in the final concentration of spheres at sationary phase, (ii) result in an asynchronous block in the budding cycle at stationary phase, (iii) completely suppress mycelium formation in two independently isolated human strains which produce low but significant levels of mycelia at stationary phase, and (iv) completely suppress mycelium formation in cultures of mutant M10, in which over 60% of the cells form mycelia at stationary phase. In contrast, micromolar concentrations of zinc do not inhibit mycelium formation induced by releasing cells from stationary-phase cultures into fresh medium at 37 degrees C. In addition, if zinc is present in the growth medium of the initial culture at 25 degrees C, the average time of subsequent mycelium formation after release into fresh medium at 37 degrees C is halved. It is demonstrated that the above effects are specific to zinc. The possibility of alterante pathways for mycelium formation is suggested, and the medical implications of this possibility are discussed.