Fungal infections are a major contributor to infectious disease-related deaths across the globe. Candida species are among the most common causes of invasive mycotic disease, with Candida albicans reigning as the leading cause of invasive candidiasis. Given that fungi are eukaryotes like their human host, the number of unique molecular targets that can be exploited for antifungal development remains limited. Currently, there are only three major classes of drugs approved for the treatment of invasive mycoses, and the efficacy of these agents is compromised by the development of drug resistance in pathogen populations. Notably, the emergence of additional drug-resistant species, such as Candida auris and Candida glabrata, further threatens the limited armamentarium of antifungals available to treat these serious infections. Here, we describe our current arsenal of antifungals and elaborate on the resistance mechanisms Candida species possess that render them recalcitrant to therapeutic intervention. Finally, we highlight some of the most promising therapeutic strategies that may help combat antifungal resistance, including combination therapy, targeting fungal-virulence traits, and modulating host immunity. Overall, a thorough understanding of the mechanistic principles governing antifungal drug resistance is fundamental for the development of novel therapeutics to combat current and emerging fungal threats.

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抗真菌药物耐药性：白色念珠菌及其以外的分子机制

真菌感染是全球传染病相关死亡的主要原因。念珠菌属是侵袭性真菌病的最常见原因之一，其中白色念珠菌是侵袭性念珠菌病的主要原因。鉴于真菌像其人类宿主一样是真核生物，可用于抗真菌开发的独特分子靶标的数量仍然有限。目前，只有三大类药物被批准用于治疗侵袭性真菌病，并且这些药物的疗效因病原体群体耐药性的发展而受到影响。值得注意的是，其他耐药物种的出现，例如耳念珠菌和光滑念珠菌，进一步威胁到可用于治疗这些严重感染的有限抗真菌药物。在这里，我们描述了我们目前的抗真菌药物库，并详细阐述了念珠菌属物种所具有的耐药机制，这些机制使它们难以接受治疗干预。最后，我们强调了一些可能有助于对抗抗真菌耐药性的最有前途的治疗策略，包括联合治疗、针对真菌毒力特征和调节宿主免疫。总体而言，彻底了解抗真菌药物耐药性的机制原理对于开发对抗当前和新兴真菌威胁的新型疗法至关重要。