Specific inhibition of acid proteinase secretion in Candida albicans by Lys-Nva-FMDP.

Secretion of aspartic (acid) proteinase by Candida albicans is inhibited by the action of a new anticandidal agent, L-lysyl-L-norvalyl-[N3-(4-methoxyfumaroyl)]-L-2,3-diamino pro panoic acid (Lys-Nva-FMDP), at low, even sub-minimum inhibitory concentrations. The observed phenomenon is a direct consequence of inhibition of the enzyme, glucosamine-6-phosphate synthase. As a result of this inhibition, biosynthesis of candidal mannoproteins is markedly reduced. A possible correlation between general inhibition of mannoprotein biosynthesis and acid proteinase secretion is suggested. The reported inhibition of acid proteinase secretion by Lys-Nva-FMDP is more specific than the previously described effects of methyl patricin, 5-fluorocytosine and fenticonazole.