Virulence of a phosphoribosylaminoimidazole carboxylase-deficient Candida albicans strain in an immunosuppressed murine model of systemic candidiasis
Virulence of a phosphoribosylaminoimidazole carboxylase-deficient Candida albicans strain in an immunosuppressed murine model of systemic candidiasis
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DOI：
10.1128/iai.69.4.2542-2548.2001
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发表时间：
2001-04-01
影响因子：
3.1
通讯作者：
Dotson, SB
中科院分区：
文献类型：
--
作者：
Donovan, M;Schumuke, JJ;Dotson, SB
在小鼠念珠菌病模型中评价了三种在ADE 2（编码磷酸核糖基氨基咪唑羧化酶的基因）功能上不同的白色念珠菌菌株的相对致病性。C.先前通过位点特异性重组构建的白色念珠菌菌株CAI 7（ade 2/ade 2）与亲本菌株CAF 2 -1和通过用野生型等位基因转化CAI 7获得的杂合ADE 2/ade 2菌株相比，在免疫抑制小鼠中是无毒力的。CAI 7毒力的降低与在没有> 10 μ g腺嘌呤/ml的外源添加的合成培养基或血清中不能增殖有关。在位点特异性破坏的ade 2位点的毒力损失，和温和型毒力的恢复与修复只有一个ade 2等位基因，证实了ADE 2基因和从头嘌呤生物合成所需的念珠菌致病性。潜在的磷酸核糖氨基咪唑羧化酶作为一个新的目标抗真菌药物的发现进行了讨论。
The relative pathogenicities of three Candida albicans strains differing in the function of ADE2 (the gene encoding phosphoribosylaminoimidazole carboxylase) were evaluated in a murine candidiasis model. C. albicans strain 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/ade2 strain 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 mug of adenine/ml. The loss of virulence upon site-specific disruption of the ade2 locus, and the restoration of mild-type virulence with the repair of just one ade2 allele, confirmed that the ADE2 gene and de novo purine biosynthesis were required for Candida pathogenicity. The potential of the phosphoribosylaminoimidazole carboxylase enzyme as a novel target for antifungal drug discovery is discussed.