Institut Pasteur, Université Paris Cité, Fungal Heterogeneity Group, Paris, France.
PLoS Pathog. 2023 Aug 31;19(8):e1011583. doi: 10.1371/journal.ppat.1011583. eCollection 2023 Aug.
Fungal infections are rising, with over 1.5 billion cases and more than 1 million deaths recorded each year. Among these, Candida infections are frequent in at-risk populations and the rapid development of drug resistance and tolerance contributes to their clinical persistence. Few antifungal drugs are available, and their efficacy is declining due to the environmental overuse and the expansion of multidrug-resistant species. One way to prolong their utility is by applying them in combination therapy. Here, we highlight recently described azole potentiators belonging to different categories: natural, repurposed, or novel compounds. We showcase examples of molecules and discuss their identified or proposed mode of action. We also emphasise the challenges in azole potentiator development, compounded by the lack of animal testing, the overreliance on Candida albicans and Candida auris, as well as the limited understanding of compound efficacy.
真菌感染正在上升,每年记录的病例超过 15 亿例,死亡人数超过 100 万。其中,在高危人群中,念珠菌感染很常见,而耐药性和耐受性的快速发展导致其临床持续存在。可用的抗真菌药物很少,由于环境过度使用和多药耐药物种的扩大,其疗效正在下降。延长其用途的一种方法是将它们应用于联合治疗。在这里,我们重点介绍属于不同类别的最近描述的唑类增效剂:天然、再利用或新型化合物。我们展示了一些分子的例子,并讨论了它们已确定或提出的作用模式。我们还强调了唑类增效剂开发所面临的挑战,包括缺乏动物试验、过度依赖白色念珠菌和耳念珠菌,以及对化合物疗效的理解有限。