The Key Laboratory of Biotechnology for Medicinal Plants of Jiangsu Province and School of Life Science, Jiangsu Normal University, Xuzhou, PR China.
Mol Microbiol. 2020 Dec;114(6):891-905. doi: 10.1111/mmi.14586. Epub 2020 Aug 18.
In recent years, the role of sphingolipids in pathogenic fungi, in terms of pathogenicity and resistance to azole drugs, has been a rapidly growing field. This review describes evidence about the roles of sphingolipids in azole resistance and fungal virulence. Sphingolipids can serve as signaling molecules that contribute to azole resistance through modulation of the expression of drug efflux pumps. They also contribute to azole resistance by participating in various microbial pathways such as the unfolded protein response (UPR), pH-responsive Rim pathway, and pleiotropic drug resistance (PDR) pathway. In addition, sphingolipid signaling and eisosomes also coordinately regulate sphingolipid biosynthesis in response to azole-induced membrane stress. Sphingolipids are important for fungal virulence, playing roles during growth in hosts under stressful conditions, maintenance of cell wall integrity, biofilm formation, and production of various virulence factors. Finally, we discuss the possibility of exploiting fungal sphingolipids for the development of new therapeutic strategies to treat infections caused by pathogenic fungi.
近年来，鞘脂类物质在致病真菌中的作用（包括致病性和唑类药物耐药性）已成为一个快速发展的领域。本文综述了鞘脂类物质在唑类耐药性和真菌毒力中的作用的相关证据。鞘脂类物质可作为信号分子，通过调节药物外排泵的表达来促进唑类耐药性。此外，鞘脂类物质还通过参与未折叠蛋白反应 (UPR)、pH 响应的 Rim 途径和多药耐药 (PDR) 途径等各种微生物途径来参与唑类耐药性。鞘脂类物质还参与了包括未折叠蛋白反应 (UPR)、pH 响应的 Rim 途径和多药耐药 (PDR) 途径等多种微生物途径，在这些途径中，它们通过调节药物外排泵的表达来促进唑类耐药性。鞘脂类物质对于真菌毒力也非常重要，在宿主压力条件下的生长、细胞壁完整性的维持、生物膜形成以及各种毒力因子的产生中发挥作用。最后，我们讨论了利用真菌鞘脂类物质开发新的治疗策略来治疗致病真菌感染的可能性。
