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Combatting the evolution of antifungal resistance in Cryptococcus neoformans.
Molecular Microbiology ( IF 2.6 ) Pub Date : 2020-07-22 , DOI: 10.1111/mmi.14565
Arianne Bermas 1 , Jennifer Geddes-McAlister 1
Affiliation  

Fungal infections are a global concern and the evolution of intrinsic resistance to current antifungals presents an alarming problem. For Cryptococcus neoformans, a human fungal pathogen of primarily immunocompromised individuals, resistance toward treatment strategies demands alternative approaches. Given the prevalence of virulence factor production during cryptococcal infection, an emerging and important field of research encompasses the development of novel antivirulence therapies proposed to improve host immune responses and promote fungal clearance. To accomplish this task, information regarding the presence and role of virulence factors, the mechanisms of action within the host, and the ability to influence fungal susceptibility to antifungals is pertinent. Research into mechanisms of antifungal resistance for C. neoformans is limited but extrapolation from successful studies in other fungal species can improve our understanding of mechanisms employed by C. neoformans and suggest targeted strategies to enhance our ability to combat the pathogen. In this Review, we highlight antifungal therapy options against Cryptococcus, explore current knowledge of underlying mechanisms promoting resistance, and present new opportunities for novel and effective strategies to overcome fungal infections and reduce, or possibly even reverse, the effects of resistance evolution.

中文翻译:

对抗新型隐球菌抗真菌耐药性的演变。

真菌感染是全球关注的问题,对当前抗真菌药物的内在耐药性的演变提出了一个令人担忧的问题。对于新型隐球菌,主要是免疫功能低下个体的人类真菌病原体,对治疗策略的抵抗需要替代方法。鉴于隐球菌感染期间毒力因子产生的普遍性,一个新兴且重要的研究领域包括开发新的抗毒力疗法,以改善宿主免疫反应和促进真菌清除。为了完成这项任务,有关毒力因子的存在和作用、宿主内的作用机制以及影响真菌对抗真菌药敏感性的能力的信息是相关的。对新型 C.抗真菌抗性机制的研究是有限的,但从其他真菌物种的成功研究中推断可以提高我们对 C.neoformans 采用的机制的理解C. neoformans并提出有针对性的策略,以增强我们对抗病原体的能力。在这篇综述中,我们重点介绍了针对隐球菌的抗真菌治疗方案,探索了促进耐药性的潜在机制的当前知识,并为克服真菌感染和减少甚至可能逆转耐药性演变的影响提供了新的有效策略的新机会。
更新日期:2020-07-22
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