EFFECT OF WATER SOLUBLE VITAMINS AND THEIR ANALOGUES ON THE GROWTH OF CANDIDA ALBICANS. I. BIOTIN, PYRIDOXAMINE, PYRIDOXINE AND FLUORINATED PYRIMIDINES.

Abstract

C. albicans showed an absolute dependency for biotin in shaker cultures in a basal mineral synthetic medium free of vitamin-precursors and vitamin-sparing amino acids. Diminished growth activity was observed with biotin sulfone and biotin diamine sulfate, but not with biocytin, N-biotinyl-β-alanine, N-biotinyl-L-aspartic ethyl ester, D-desthiobiotin or biotin-D-sulfoxide. The ability of the organism to utilize desthiobiotin indicates that its block in biosynthesis of biotin occurs at a step prior to desthiobiotin biosynthesis. Pyridoxamine and pyridoxine were both highly growth stimulatory at 1000 and 2056 µg/ml but not in the vitamin range at 1 to 10 µg/ml. Since desoxypyridoxine compounds failed to inhibit growth in the absence of B6, it was concluded thatC. albicans has no dependency for vitamin B6, although it actively metabolizes it. Pyridoxamine shortened the lag phase of the organism and reversed the toxicity of 5-fluorouracil and 5-fluoro-2′-deoxyuridine, pointing to a new role of vitamin B6 in nucleic acid metabolism of the organism. Inhibition indices for pyridoxamine and pyridoxine versus FU and FUDR were inconstant, indicating that the antagonism with the fluoropyrimidines was non-competitive in nature and the B6 competes with these compounds at more than one site on the cell.