Increased high-affinity phosphodiesterase PDE2 gene expression in germ tubes counteracts CAP1-dependent synthesis of cyclic AMP, limits hypha production and promotes virulence of Candida albicans
Increased high-affinity phosphodiesterase PDE2 gene expression in germ tubes counteracts CAP1-dependent synthesis of cyclic AMP, limits hypha production and promotes virulence of Candida albicans
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DOI：
10.1046/j.1365-2958.2003.03692.x
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发表时间：
2003-10-01
影响因子：
3.6
通讯作者：
Sundstrom, P
中科院分区：
文献类型：
--
作者：
Bahn, YS;Staab, J;Sundstrom, P
酵母菌、假菌丝和真菌丝之间的频繁相互转化是白色念珠菌在哺乳动物组织中生长的标志。产生真正的菌丝，Hwp 1和毒力的瞬时CAP 1依赖性脉冲cAMP的要求提出了关于酵母菌和假菌丝形式在念珠菌病发病机制中的作用的问题。在这项研究中，超丝状突变体，在他们的能力有限，产生芽，通过破坏高亲和力磷酸二酯酶基因PDE 2。PDE 2基因产物对cAMP的降解通过PDE 2/PDE 2突变体中更高的基础cAMP水平和通过cAMP的积累至允许芽管形成的水平（在破坏Cap 1/Cap 1突变体中的PDE 2后）来证实。C.白念珠菌和酿酒酵母的pde 2/pde 2突变体，包括营养饥饿和外源性cAMP的敏感性和缺陷进入稳定期。重要的是，在系统性念珠菌病模型中，超丝状突变体与亚丝状突变体一样无毒力。多种形式的生长似乎是由cAMP合成和降解的紧密耦合控制的毒力属性。在芽管诱导条件下，cAMP缺陷型cap 1/cap 1突变体中PDE 2 mRNA的延迟增加表明了一种涉及cAMP依赖性PDE 2 mRNA诱导的控制机制。
Frequent interconversion between yeasts, pseudohyphae and true hyphae is a hallmark of Candida albicans growth in mammalian tissues. The requirement for transient CAP1-dependent pulses of cAMP for generating true hyphae, Hwp1 and virulence raises questions about the role of yeast and pseudohyphal forms in the pathogenesis of candidiasis. In this study, hyperfilamentous mutants, limited in their capacity to produce buds, were generated by disrupting the high-affinity phosphodiesterase gene PDE2. Degradation of cAMP by the PDE2 gene product was confirmed by higher basal cAMP levels in the pde2/pde2 mutant and by accumulation of cAMP to levels permitting germ tube formation upon disrupting PDE2 in the cap1/cap1 mutant. Similar phenotypes of the C. albicans and Saccharomyces cerevisiae pde2/pde2 mutants were found, including sensitivity to nutritional starvation and exogenous cAMP and defective entry into stationary phase. Importantly, the hyperfilamentous mutants were as avirulent as hypofilamentous mutants in a systemic model of candidiasis. Growth in a multiplicity of forms appears to be a virulence attribute that is controlled by tight coupling of cAMP synthesis and degradation. Delayed increases in PDE2 mRNA in cAMP-deficient cap1/cap1 mutants during germ tube-inducing conditions suggested a mechanism of control involving cAMP-dependent induction of PDE2 mRNA.