Sharma Jehoshua, Rosiana Sierra, Razzaq Iqra, Shapiro Rebecca S
Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON N1G 2W1, Canada.
J Fungi (Basel). 2019 Feb 21;5(1):17. doi: 10.3390/jof5010017.
Fungal infections are a growing public health concern, and an increasingly important cause of human mortality, with species being amongst the most frequently encountered of these opportunistic fungal pathogens. Several species are polymorphic, and able to transition between distinct morphological states, including yeast, hyphal, and pseudohyphal forms. While not all pathogens are polymorphic, the ability to undergo morphogenesis is linked with the virulence of many of these pathogens. There are also many connections between morphogenesis and antifungal drug treatment and susceptibility. Here, we review how morphogenesis-a key virulence trait-is linked with antifungal drugs and antifungal drug resistance. We highlight how antifungal therapeutics are able to modulate morphogenesis in both sensitive and drug-resistant strains, the shared signaling pathways that mediate both morphogenesis and the cellular response to antifungal drugs and drug resistance, and the connection between morphology, drug resistance, and biofilm growth. We further review the development of anti-virulence drugs, and targeting morphogenesis as a novel therapeutic strategy to target fungal pathogens. Together, this review highlights important connections between fungal morphogenesis, virulence, and susceptibility to antifungals.
真菌感染正日益引起公共卫生关注，并且是导致人类死亡的一个愈发重要的原因，其中某些物种是这些机会性真菌病原体中最常遇到的。几种物种具有多态性，能够在不同的形态状态之间转变，包括酵母、菌丝和假菌丝形态。虽然并非所有病原体都是多态性的，但进行形态发生的能力与许多这些病原体的毒力相关。形态发生与抗真菌药物治疗及易感性之间也存在许多联系。在此，我们综述形态发生——一种关键的毒力特征——如何与抗真菌药物及抗真菌药物耐药性相关联。我们强调抗真菌治疗如何能够在敏感菌株和耐药菌株中调节形态发生，介导形态发生以及细胞对抗真菌药物和耐药性反应的共同信号通路，以及形态、耐药性和生物膜生长之间的联系。我们进一步综述抗毒力药物的研发，以及将靶向形态发生作为一种针对真菌病原体的新型治疗策略。总之，本综述突出了真菌形态发生、毒力和抗真菌药物易感性之间的重要联系。
