Reductive iron uptake by Candida albicans:: role of copper, iron and the TUP1 regulator
Reductive iron uptake by Candida albicans:: role of copper, iron and the TUP1 regulator
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DOI：
10.1099/00221287-148-1-29
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发表时间：
2002-01-01
期刊：
影响因子：
2.8
通讯作者：
Dancis, A
中科院分区：
文献类型：
--
作者：
Knight, SAB;Lesuisse, E;Dancis, A
机会性病原体白色念珠菌中的亚铁渗透酶对铁的高亲和力吸收是其毒力所必需的。在此，通过研究三种不同的活性来表征该铁吸收系统：外部定向的表面三价铁还原酶、膜相关的 PPD（对苯二胺）氧化酶和细胞亚铁转运活性。 PPD 氧化酶和亚铁运输活动需要铜。相比之下，铁载体吸收铁不需要铜。在生长培养基中添加铁会抑制铁还原酶和亚铁转运，表明体内平衡调节。为了鉴定所涉及的基因，用白色念珠菌基因组文库转化了酿酒酵母的直系同源突变体。 CFL95 是一种与三价铁还原酶序列相似的基因，可恢复直系同源酿酒酵母突变体的还原酶活性。 CaFTR2 和 CaFTR1 是与亚铁渗透酶同源的基因，赋予直系同源酿酒酵母突变体亚铁转运活性。然而，基因组文库和 CaFET99（多铜氧化酶同源物和 PPD 氧化酶候选基因）都不能补充酿酒酵母突变体，可能是因为靶向或组装问题。 CF195、CaFTR1 和 CaFET99 的转录本受到铁的强烈抑制，而 CaFTR2 的转录本则受到铁的诱导。 TUP1 调节器的缺失扰乱了还原性铁吸收的稳态控制。顺便说一句，缺铁会诱导黄素产生，但在缺乏 TUP1 控制的情况下，黄素的产生会被错误调节。两个铁渗透酶基因的相反调节和 TUP1 的作用表明，白色念珠菌获取铁的过程可能比酿酒酵母更复杂，也可能更具适应性。
High-affinity iron uptake by a ferrous permease in the opportunistic pathogen Candida albicans is required for virulence. Here this iron uptake system has been characterized by investigating three distinct activities: an externally directed surface ferric reductase, a membrane-associated PPD (p-phenylenediamine) oxidase and a cellular ferrous iron transport activity. Copper was required for the PPD oxidase and ferrous transport activities. In contrast, copper was not required for iron uptake from siderophores. Addition of iron to the growth medium repressed ferric reductase and ferrous transport, indicating homeostatic regulation. To identify the genes involved, orthologous mutants of Saccharomyces cerevisiae were transformed with a genomic library of C. albicans. CFL95, a gene with sequence similarity to ferric reductases, restored reductase activity to the orthologous S. cerevisiae mutant. CaFTR2 and CaFTR1, genes with homology to ferrous permeases, conferred ferrous transport activity to the orthologous S. cerevisiae mutant. However, neither a genomic library nor CaFET99, a multicopper oxidase homologue and candidate gene for the PPD oxidase, complemented the S. cerevisiae mutant, possibly because of problems with targeting or assembly. Transcripts for CF195, CaFTR1 and CaFET99 were strongly repressed by iron, whereas the CaFTR2 transcript was induced by iron. Deletion of the TUP1 regulator perturbed the homeostatic control of reductive iron uptake. Incidentally, iron starvation was noted to induce flavin production and this was misregulated in the absence of TUP1 control. The opposite regulation of two iron permease genes and the role of TUP1 indicate that the process of iron acquisition by C. albicans may be more complex and potentially more adaptable than by S. cerevisiae.