Decreased activity of UMP pyrophosphorylase associated with resistance to 5-fluorocytosine in Candida albicans

Abstract

UMP pyrophosphorylase activity was assayed in crude lysates prepared from Candida albicans. Specific activity of UMP pyrophosphorylase was high in clinical isolates which were susceptible to 5-fluorocytosine. Resistant clinical isolates displayed low activity, and partially resistant (heterozygous) isolates displayed intermediate activity. Segregation from the heterozygous state resulted in a homozygous susceptible segregant with high UMP pyrophosphorylase activity and a homozygous resistant segregant with low activity. The observed specific activities were consistent with the hypothesis that specific activity was determined by the sum of the activities due to the dominant (FCY) and recessive (fcy) alleles of the resistance gene. Strains which possessed little UMP pyrophosphorylase activity released uracil into the medium when grown in the absence of 5-fluorocytosine; this result suggested that recycling of intracellular uracil is a normal function of this enzyme.