Pseudohyphal Regulation by the Transcription Factor Rfg1p in Candida albicans
Pseudohyphal Regulation by the Transcription Factor Rfg1p in Candida albicans
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DOI：
10.1128/ec.00088-10
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发表时间：
2010-09-01
期刊：
影响因子：
--
通讯作者：
Saville, Stephen P.
中科院分区：
文献类型：
--
作者：
Cleary, Ian A.;Mulabagal, Priyadarshini;Saville, Stephen P.
机会性人类真菌病原体白色念珠菌是医院感染的主要原因。C.白色念珠菌的发病机制是酵母菌到菌丝的转变。菌丝的形成受到转录因子如Efg 1 p和Cph 1 p的正向控制，这些因子是菌丝生长所必需的，而Tup 1 p、Rfg 1 p和Nrg 1 p则是负向控制。我们小组以前的工作表明，调节NRG 1基因表达，从而改变形态，与C。白色念珠菌导致疾病。为了进一步剖析这些毒力机制，我们采用相同的策略来分析Rfg 1 p在表达和毒力中的作用。使用tet-RFG 1菌株的研究显示，RFG 1过表达在体外或在血源性播散性念珠菌病的小鼠模型中不抑制菌丝形成。有趣的是，RFG 1的过表达在酵母生长条件下驱动假菌丝的形成--一种与C.几种有丝分裂调控基因之一发生突变的白色念珠菌菌株。互补试验和实时PCR分析表明，虽然tet-RFG 1菌株的形态类似于有丝分裂调节突变体，但Rfg 1 p过表达不影响这些基因的表达。
The opportunistic human fungal pathogen Candida albicans is a major cause of nosocomial infections. One of the fundamental features of C. albicans pathogenesis is the yeast-to-hypha transition. Hypha formation is controlled positively by transcription factors such as Efg1p and Cph1p, which are required for hyphal growth, and negatively by Tup1p, Rfg1p, and Nrg1p. Previous work by our group has shown that modulating NRG1 gene expression, hence altering morphology, is intimately linked to the capacity of C. albicans to cause disease. To further dissect these virulence mechanisms, we employed the same strategy to analyze the role of Rfg1p in filamentation and virulence. Studies using a tet-RFG1 strain revealed that RFG1 overexpression does not inhibit hypha formation in vitro or in the mouse model of hematogenously disseminated candidiasis. Interestingly, RFG1 overexpression drives formation of pseudohyphae under yeast growth conditions-a phenotype similar to that of C. albicans strains with mutations in one of several mitotic regulatory genes. Complementation assays and real-time PCR analysis indicate that, although the morphology of the tet-RFG1 strain resembles that of the mitotic regulator mutants, Rfg1p overexpression does not impact expression of these genes.