Invasive fungal infections cause significant morbidity and mortality in part due to a limited antifungal drug arsenal. One therapeutic challenge faced by clinicians is the significant host toxicity associated with antifungal drugs. Another challenge is the fungistatic mechanism of action of some drugs. Consequently, the identification of fungus-specific drug targets essential for fitness in vivo remains a significant goal of medical mycology research. The trehalose biosynthetic pathway is found in a wide variety of organisms, including human-pathogenic fungi, but not in humans. Genes encoding proteins involved in trehalose biosynthesis are mechanistically linked to the metabolism, cell wall homeostasis, stress responses, and virulence of Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus. While there are a number of pathways for trehalose production across the tree of life, the TPS/TPP (trehalose-6-phosphate synthase/trehalose-6-phosphate phosphatase) pathway is the canonical pathway found in human-pathogenic fungi. Importantly, data suggest that proteins involved in trehalose biosynthesis play other critical roles in fungal metabolism and in vivo fitness that remain to be fully elucidated. By further defining the biology and functions of trehalose and its biosynthetic pathway components in pathogenic fungi, an opportunity exists to leverage this pathway as a potent antifungal drug target. The goal of this review is to cover the known roles of this important molecule and its associated biosynthesis-encoding genes in the human-pathogenic fungi studied to date and to employ these data to critically assess the opportunities and challenges facing development of this pathway as a therapeutic target.

中文翻译：

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海藻糖生物合成途径在人类真菌感染的发病机理中的核心作用：治疗发展的机遇与挑战。

侵袭性真菌感染会导致很大的发病率和死亡率，部分原因是抗真菌药库数量有限。临床医生面临的治疗挑战之一是与抗真菌药有关的明显的宿主毒性。另一个挑战是某些药物的抑真菌作用机理。因此，鉴定对于体内适应性必不可少的真菌特异性药物靶标仍然是医学真菌学研究的重要目标。海藻糖的生物合成途径存在于多种生物中，包括人类致病性真菌，但在人类中却没有。编码参与海藻糖生物合成的蛋白质的基因在机械上与白色念珠菌，新隐球菌和烟曲霉的代谢，细胞壁稳态，应激反应和毒力相关。虽然生命树中有许多生产海藻糖的途径，但是TPS / TPP（海藻糖6磷酸合酶/海藻糖6磷酸磷酸酶）途径是人类致病真菌中的典型途径。重要的是，数据表明，参与海藻糖生物合成的蛋白质在真菌代谢和体内适应性中起着其他关键作用，而这些作用还有待充分阐明。通过进一步定义海藻糖及其在致病性真菌中的生物合成途径组分的生物学和功能，存在利用这种途径作为有效的抗真菌药物靶标的机会。