Fungal susceptibility to zinc deprivation

Calprotectin is a neutrophil-derived antimicrobial protein that competes with microorganisms for zinc. The zinc-specific effect of calprotectin against Candida albicans appears to be related to this organism's marked susceptibility to deprivation of this metal. However, it is not known whether this susceptibility is particular to C albicans or whether it is a characteristic of pathogenic fungi in general. As a means of deciding between these 2 possibilities, we undertook the study reported here to compare the susceptibility to zinc deprivation of 6 other pathogenic fungal species in addition to that of C albicans . We tested the effect of metals in reversing growth inhibition of the 7 fungi against abscess-fluid supernatant (a source of calprotectin) and 3 chemical chelators. Data were expressed as the concentration of metal required to bring about 50% restoration of growth. Zinc was found to be much more potent than the other metals tested in reversing growth inhibition of all the organisms by human abscess fluid and all 3 chemical chelators. Copper and manganese also had some effect. In some cases, chelator stability constants were higher for other metals than for zinc; in particular, although diethylenetriaminopentaacetic acid has a stability constant for iron almost 10(10) times greater than that for zinc, zinc was more effective than iron in reversing growth inhibition by this chelator against all of the organisms. These results suggest that marked susceptibility to zinc deprivation is a general characteristic of pathogenic fungi.