DISRUPTION OF THE CANDIDA-ALBICANS TPS1 GENE ENCODING TREHALOSE-6-PHOSPHATE SYNTHASE IMPAIRS FORMATION OF HYPHAE AND DECREASES INFECTIVITY

The TPS1 gene from Candida albicans, which encodes trehalose-6-phospha te synthase, has been cloned by functional complementation of a tps1 m utant from Saccharomyces cerevisiae, In contrast with the wild-type st rain, the double tps1/tps1 disruptant did not accumulate trehalose at stationary phase or after heat shock. Growth of the tps1/tps1 disrupta nt at 30 degrees C was indistinguishable from that of the wild type. H owever, at 42 degrees C it did not grow on glucose or fructose but gre w normally on galactose or glycerol. At 37 degrees C, the yeast-hypha transition in the mutant in glucose-calf serum medium did not occur. D uring growth at 42 degrees C, the mutant did not form hyphae in galact ose or in glycerol, Some of the growth defects observed may be traced to an unbalanced sugar metabolism that reduces the cellular content of ATP, Mice inoculated with 10(6) CFU of the tps1/tps1 mutant did not s how visible symptoms of infection 16 days after inoculation, while tho se similarly inoculated with wild-type cells were dead 12 days after i noculation.