School of Pharmaceutical Sciences, Shandong University, Jinan, China.
Intensive Care Unit, Qianfoshan Hospital Affiliated to Shandong University, Jinan, China.
Front Cell Infect Microbiol. 2017 Dec 19;7:520. doi: 10.3389/fcimb.2017.00520. eCollection 2017.
In recent decades, the incidence of invasive fungal infections has increased notably. , a common opportunistic fungal pathogen that dwells on human mucosal surfaces, can cause fungal infections, especially in immunocompromised and high-risk surgical patients. In addition, the wide use of antifungal agents has likely contributed to resistance of to traditional antifungal drugs, increasing the difficulty of treatment. Thus, it is urgent to identify novel antifungal drugs to cope with infections. Heat shock proteins (Hsps) exist in most organisms and are expressed in response to thermal stress. In , Hsps control basic physiological activities or virulence via interaction with a variety of diverse regulators of cellular signaling pathways. Moreover, it has been demonstrated that Hsps confer drug resistance to . Many studies have shown that disrupting the normal functions of Hsps inhibits fungal growth or reverses the tolerance of to traditional antifungal drugs. Here, we review known functions of the diverse Hsp family, Hsp-associated intracellular signaling pathways and potential antifungal targets based on these pathways in . We hope this review will aid in revealing potential new roles of Hsps in addition to canonical heat stress adaptions and provide more insight into identifying potential novel antifungal targets.
近几十年来,侵袭性真菌感染的发病率显著增加。白色念珠菌是一种常见的机会性真菌病原体,栖息在人类黏膜表面,可引起真菌感染,特别是在免疫功能低下和高风险手术患者中。此外,抗真菌药物的广泛使用可能导致白色念珠菌对传统抗真菌药物产生耐药性,增加了治疗的难度。因此,迫切需要寻找新型抗真菌药物来应对白色念珠菌感染。热休克蛋白(Hsps)存在于大多数生物体中,并在受到热应激时表达。在白色念珠菌中,Hsps 通过与多种不同的细胞信号通路调节剂相互作用来控制基本的生理活动或毒力。此外,已经证明 Hsps 使白色念珠菌对药物产生耐药性。许多研究表明,破坏白色念珠菌 Hsps 的正常功能可以抑制真菌生长或逆转其对传统抗真菌药物的耐受性。在这里,我们综述了白色念珠菌中不同 Hsp 家族、Hsp 相关的细胞内信号通路以及基于这些通路的潜在抗真菌靶点的已知功能。我们希望本综述将有助于揭示白色念珠菌 Hsps 的潜在新作用,除了经典的热应激适应外,并为确定潜在的新型抗真菌靶点提供更多的见解。