School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
J Biol Chem. 2024 Jul;300(7):107444. doi: 10.1016/j.jbc.2024.107444. Epub 2024 Jun 4.
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.
白色念珠菌是一种机会性真菌病原体，它可以根据所接收到的环境线索在酵母和菌丝形态之间切换。向菌丝形态的转变对于建立侵袭性感染至关重要。菌丝形态的特征还在于细胞表面表达菌丝特异性蛋白，其中许多是 GPI-锚定的，是其毒力的重要决定因素。菌丝形态发生和 GPI 锚定蛋白表达之间的协调是通过真菌中 GPI 生物合成和 cAMP-PKA 信号级联之间的有趣串扰来实现的；在其人类宿主中未发现平行相互作用。另一方面，在非致病性酵母酿酒酵母中，当菌丝形成被激活时，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 信号之间的串扰来实现的。如何从普遍存在于真核生物中的两个相当保守的途径之间的串扰中获得截然相反的效果？本综述试图提供一个模型来解释这些差异。为此，它首先为感兴趣的读者概述了这两个途径，重点介绍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，然后解释了如何实现不同的调节机制。虽然共性使人们能够开发出一般性理论，但希望采取更细致入微的方法，考虑到物种特异性差异，能够对这些过程有特定于生物体的理解，并有助于开发靶向治疗方法。
