PDF(Pubmed)
Abstract：
Candida albicans is an opportunistic fungal pathogen that can switch between yeast and hyphal morphologies depending on the environmental cues it receives. The switch to hyphal form is crucial for the establishment of invasive infections. The hyphal form is also characterized by the cell surface expression of hyphae-specific proteins, many of which are GPI-anchored and important determinants of its virulence. The coordination between hyphal morphogenesis and the expression of GPI-anchored proteins is made possible by an interesting cross-talk between GPI biosynthesis and the cAMP-PKA signaling cascade in the fungus; a parallel interaction is not found in its human host. On the other hand, in the nonpathogenic yeast, Saccharomyces cerevisiae, GPI biosynthesis is shut down when filamentation is activated and vice versa. This too is achieved by a cross-talk between GPI biosynthesis and cAMP-PKA signaling. How are diametrically opposite effects obtained from the cross-talk between two reasonably well-conserved pathways present ubiquitously across eukarya? This Review attempts to provide a model to explain these differences. In order to do so, it first provides an overview of the two pathways for the interested reader, highlighting the similarities and differences that are observed in C. albicans versus the well-studied S. cerevisiae model, before going on to explain how the different mechanisms of regulation are effected. While commonalities enable the development of generalized theories, it is hoped that a more nuanced approach, that takes into consideration species-specific differences, will enable organism-specific understanding of these processes and contribute to the development of targeted therapies.
摘要：
白色念珠菌是一种机会性真菌病原体，可以根据其接收的环境线索在酵母和菌丝形态之间切换。转变为菌丝形式对于建立侵袭性感染至关重要。菌丝形式的特征还在于菌丝特异性蛋白的细胞表面表达，其中许多是GPI锚定的，是其毒力的重要决定因素。真菌中GPI生物合成与cAMP-PKA信号级联之间的有趣交叉对话使菌丝形态发生与GPI锚定蛋白表达之间的协调成为可能；在其人类宿主中未发现平行相互作用。另一方面,在非致病性酵母中，酿酒酵母，当成丝被激活时,GPI生物合成被关闭,反之亦然。这也是通过GPI生物合成和cAMP-PKA信号之间的串扰实现的。如何从两个相当保守的途径之间的交叉对话中获得截然相反的效果？这篇评论试图提供一个模型来解释这些差异。为了做到这一点,它首先为感兴趣的读者提供了两种途径的概述，突出了在白色念珠菌与经过充分研究的酿酒酵母模型中观察到的相似性和差异，在继续解释不同的监管机制是如何影响的之前。虽然共性使广义理论的发展成为可能，但人们希望采用更细微的方法，这考虑到了特定物种的差异，将使生物体对这些过程的特定理解，并有助于靶向治疗的发展。
