Nguyen Stephanie, Truong Jia Q, Bruning John B
Institute of Photonics and Advanced Sensing (IPAS), School of Biological Sciences, The University of Adelaide, Adelaide, SA, Australia.
School of Biological Sciences, The University of Adelaide, Adelaide, SA, Australia.
Front Mol Biosci. 2021 Jan 12;7:621366. doi: 10.3389/fmolb.2020.621366. eCollection 2020.
The impact of invasive fungal infections on human health is a serious, but largely overlooked, public health issue. Commonly affecting the immunocompromised community, fungal infections are predominantly caused by species of , and . Treatments are reliant on the aggressive use of pre-existing antifungal drug classes that target the fungal cell wall and membrane. Despite their frequent use, these drugs are subject to unfavorable drug-drug interactions, can cause undesirable side-effects and have compromised efficacy due to the emergence of antifungal resistance. Hence, there is a clear need to develop novel classes of antifungal drugs. A promising approach involves exploiting the metabolic needs of fungi by targeted interruption of essential metabolic pathways. This review highlights potential antifungal targets including enolase, a component of the enolase-plasminogen complex, and enzymes from the mannitol biosynthesis and purine nucleotide biosynthesis pathways. There has been increased interest in the enzymes that comprise these particular pathways and further investigation into their merits as antifungal targets and roles in fungal survival and virulence are warranted. Disruption of these vital processes by targeting unconventional pathways with small molecules or antibodies may serve as a promising approach to discovering novel classes of antifungals.
侵袭性真菌感染对人类健康的影响是一个严重但在很大程度上被忽视的公共卫生问题。真菌感染通常影响免疫功能低下人群，主要由 、 和 的某些物种引起。治疗依赖于积极使用针对真菌细胞壁和细胞膜的现有抗真菌药物类别。尽管这些药物经常使用，但它们存在不良的药物相互作用，会引起不良副作用，并且由于抗真菌耐药性的出现而疗效受损。因此，显然需要开发新型抗真菌药物。一种有前景的方法是通过有针对性地中断基本代谢途径来利用真菌的代谢需求。本综述重点介绍了潜在的抗真菌靶点，包括烯醇化酶（烯醇化酶 - 纤溶酶原复合物的一个组成部分）以及来自甘露醇生物合成和嘌呤核苷酸生物合成途径的酶。人们对构成这些特定途径的酶的兴趣日益增加，有必要进一步研究它们作为抗真菌靶点的优点以及在真菌存活和毒力中的作用。通过用小分子或抗体靶向非常规途径来破坏这些重要过程，可能是发现新型抗真菌药物的一种有前景的方法。
