Virulence of a Phosphoribosylaminoimidazole Carboxylase-DeficientCandidaalbicansStrain in an Immunosuppressed Murine Model of Systemic Candidiasis

ABSTRACTThe relative pathogenicities of three Candida albicansstrains differing in the function ofADE2(the gene encoding phosphoribosylaminoimidazole carboxylase) were evaluated in a murine candidiasis model. C. albicansstrain CAI7 (ade2/ade2), previously constructed by site-specific recombination, was avirulent in immunosuppressed mice compared to the parent strain, CAF2-1, and a heterozygous ADE2/ade2strain obtained by transforming CAI7 with a wild-type allele. The reduced virulence of CAI7 was correlated with the inability to proliferate in either synthetic medium or serum without the exogenous addition of >10 μg of adenine/ml. The loss of virulence upon site-specific disruption of the ade2locus, and the restoration of wild-type virulence with the repair of just one ade2allele, confirmed that the ADE2gene and de novo purine biosynthesis were required for Candidapathogenicity. The potential of the phosphoribosylaminoimidazole carboxylase enzyme as a novel target for antifungal drug discovery is discussed.