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Abstract：
The World Health Organization (WHO) recently published a list of fungal priority pathogens, including Candida albicans and C. auris. The increased level of resistance of Candida is raising concern, considering the availability of only four classes of medicine. The WHO is seeking novel agent classes with different targets and mechanisms of action. Targeting Candida metacaspases to control intrinsic cell death could provide new therapeutic opportunities for invasive candidiasis. In this review, we provide the available evidence for Candida cell death, describe Candida metacaspases, and discuss the potential of Candida metacaspases to offer a new specific target. Targeting Candida cell death has good scientific rationale given that the fungicidal activity of many marketed antifungals is mediated, among others, by cell death triggering. But none of the available antifungals are specifically activating Candida metacaspases, making this target a new therapeutic opportunity for non-susceptible isolates. It is expected that antifungals based on the activation of fungi metacaspases will have a broad spectrum of action, as metacaspases have been described in many fungi, including filamentous fungi. Considering this original mechanism of action, it could be of great interest to combine these new antifungal candidates with existing antifungals. This approach would help to avoid the development of antifungal resistance, which is especially increasing in Candida.
摘要：
世界卫生组织（WHO）最近公布了一份真菌优先病原体名单，包括白色念珠菌和C.auris。念珠菌耐药性的增加引起了人们的关注，考虑到只有四类药物的可用性。WHO正在寻找具有不同目标和作用机制的新型药剂类别。靶向念珠菌谷冬酶以控制内在细胞死亡可能为侵袭性念珠菌病提供新的治疗机会。在这次审查中,我们提供了念珠菌细胞死亡的现有证据,描述念珠菌谷冬酶，并商量了假丝酵母β-胱天蛋白酶的潜力，为其提供一个新的特异性靶点。靶向念珠菌细胞死亡具有良好的科学原理，因为许多市售抗真菌剂的杀菌活性是介导的，其中,细胞死亡触发。但是现有的抗真菌药物都没有特异性激活念珠菌的β-半胱氨酸蛋白酶,使此靶标成为非易感分离株的新治疗机会。预计基于真菌的激活的抗真菌药物将具有广泛的作用，正如在许多真菌中已经描述的，包括丝状真菌。考虑到这种原始的作用机制，将这些新的抗真菌候选药物与现有的抗真菌药物结合起来可能会引起极大的兴趣。这种方法将有助于避免抗真菌耐药性的发展，在念珠菌中尤其增加。
