ABSTRACT

Candida albicans typically resides in the human gastrointestinal tract and mucosal membranes as a commensal organism. To adapt and cope with the host immune system, it has evolved a variety of mechanisms of adaptation such as stress-induced mutagenesis and epigenetic regulation. Niche-specific patterns of gene expression also allow the fungus to fine-tune its response to specific microenvironments in the host and switch from harmless commensal to invasive pathogen. Proteome plasticity produced by CUG ambiguity, on the other hand is emerging as a new layer of complexity in C. albicans adaptation, pathogenesis, and drug resistance. Such proteome plasticity is the result of a genetic code alteration where the leucine CUG codon is translated mainly as serine (97%), but maintains some level of leucine (3%) assignment. In this review, we dissect the link between C. albicans non-standard CUG translation, proteome plasticity, host adaptation and pathogenesis. We discuss published work showing how this pathogen uses the fidelity of protein synthesis to spawn novel virulence traits.

中文翻译：

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非标准翻译在白色念珠菌发病机制中的作用

摘要

白色念珠菌通常作为共生生物存在于人类胃肠道和粘膜中。为了适应和应对宿主免疫系统，它已经进化出多种适应机制，例如应激诱导的诱变和表观遗传调控。特定于生态位的基因表达模式还允许真菌微调其对宿主特定微环境的反应，并从无害的共生病原体转变为侵入性病原体。另一方面，由 CUG 模糊性产生的蛋白质组可塑性正在成为白色念珠菌中新的复杂层适应、发病机制和耐药性。这种蛋白质组可塑性是遗传密码改变的结果，其中亮氨酸 CUG 密码子主要翻译为丝氨酸 (97%)，但保持一定水平的亮氨酸 (3%) 分配。在这篇综述中，我们剖析了白色念珠菌非标准 CUG 翻译、蛋白质组可塑性、宿主适应和发病机制之间的联系。我们讨论了已发表的工作，展示了这种病原体如何利用蛋白质合成的保真度来产生新的毒力特征。