ATTENUATED VIRULENCE OF URIDINE-URACIL AUXOTROPHS OF ASPERGILLUS-FUMIGATUS

Aspergillus fumigatus mutants that are deficient in the de novo UR IP biosynthesis pathway because of a mutation in the pyrG gene encoding o rotidine-5'-phosphate decarboxylase (and therefore auxotrophic for uri dine or uracil) were evaluated in a murine model of invasive aspergill osis. These mutants were entirely nonpathogenic, and mutant conidia re mained ungerminated in alveolar macrophages. Both the germination and virulence defects could be restored by supplementing the drinking wate r of the animals with uridine. DNA-mediated transformation of one of t he pyrG mutants with the Aspergillus niger pyrG gene also restored vir ulence. These results suggest that uridine and uracil are limiting in the lung environment, thus preventing conidium germination and hence v irulence of the pyrG mutants.