Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029, Urbino, PU, Italy.
Appl Microbiol Biotechnol. 2024 Jan 19;108(1):147. doi: 10.1007/s00253-023-12884-8.
Fungal infections represent a serious global health threat. The new emerging pathogens and the spread of different forms of resistance are now hardly challenging the tools available in therapy and diagnostics. With the commonly used diagnoses, fungal identification is often slow and inaccurate, and, on the other hand, some drugs currently used as treatments are significantly affected by the decrease in susceptibility. Herein, the antifungal arsenal is critically summarized. Besides describing the old approaches and their mechanisms, advantages, and limitations, the focus is dedicated to innovative strategies which are designed, identified, and developed to take advantage of the discrepancies between fungal and host cells. Relevant pathways and their role in survival and virulence are discussed as their suitability as sources of antifungal targets. In a similar way, molecules with antifungal activity are reported as potential agents/precursors of the next generation of antimycotics. Particular attention was devoted to biotechnological entities, to their novelty and reliability, to drug repurposing and restoration, and to combinatorial applications yielding significant improvements in efficacy. KEY POINTS: • New antifungal agents and targets are needed to limit fungal morbidity and mortality. • Therapeutics and diagnostics suffer of delays in innovation and lack of targets. • Biologics, drug repurposing and combinations are the future of antifungal treatments.
真菌感染是一个严重的全球健康威胁。新出现的病原体和不同形式的耐药性传播，使得治疗和诊断中现有的工具几乎难以应对。由于常用的诊断方法，真菌鉴定往往缓慢且不准确，另一方面，一些目前用作治疗的药物受到耐药性降低的显著影响。本文批判性地总结了抗真菌药物。除了描述旧方法及其机制、优点和局限性外，重点还在于设计、鉴定和开发创新策略，以利用真菌细胞和宿主细胞之间的差异。讨论了相关途径及其在生存和毒力中的作用，因为它们适合作为抗真菌靶点的来源。同样，具有抗真菌活性的分子被报道为下一代抗真菌药物的潜在药物/前体。特别关注生物技术实体，其新颖性和可靠性，药物再利用和修复，以及组合应用，在疗效方面取得了显著提高。关键点：• 需要新的抗真菌药物和靶标来限制真菌感染的发病率和死亡率。• 治疗和诊断在创新和缺乏靶标方面存在滞后。• 生物制剂、药物再利用和联合用药是抗真菌治疗的未来。
