DIFFERENTIAL SUSCEPTIBILITY OF YEAST AND HYPHAL FORMS OF CANDIDA-ALBICANS TO MACROPHAGE-DERIVED NITROGEN-CONTAINING COMPOUNDS

Candida albicans is a dimorphic Fungus capable of transition from the yeast form (Y-Candida) to the hyphal form (H-Candida). Both Y-Candida and H-Candida are known to be growth inhibited by murine macrophages ( M phi) in vitro. In the present report, we demonstrate that M phi expo sed to interferon gamma (IFN-gamma) plus lipopolysaccharide (LPS) show enhanced anti-Y-Candida and anti-H-Candida activities. To further inv estigate the phenomenon, Y-Candida and H-Candida were assessed for sus ceptibilities to M phi-derived supernatants. Only the growth of H-Cand ida, and not that of Y-Candida, is impaired by cell-free supernatants from M phi, treated with IFN-gamma plus LPS. In contrast, no H-Candida growth inhibition occurs when supernatants from M phi exposed to IFN- gamma plus LPS in the presence of N-G-monomethyl-L-arginine, an inhibi tor of nitric oxide (NO) synthesis, are employed. Finally, supernatant s from M phi incubated with sodium nitroprusside, an NO-generating age nt, also show anti-H-Candida activity, In conclusion, these results in dicate that H-Candida but not Y-Candida is susceptible to extracellula r antifungal mechanisms employed by M phi, which likely involve stable nitrogen-containing compounds.