School of Pharmaceutical Sciences, Shandong University, Jinan, China.
Department of Pharmacy, Feicheng Mining Central Hospital, Feicheng, China.
Front Cell Infect Microbiol. 2018 Sep 4;8:286. doi: 10.3389/fcimb.2018.00286. eCollection 2018.
In recent decades, invasive fungal infections have been increasing significantly, contributing to high incidences and mortality in immunosuppressed patients. () is the most prevalent opportunistic fungal pathogen in humans that can cause severe and often fatal bloodstream infections. Current antifungal agents have several limitations, including that only a small number of classes of antifungals are available, certain of which have severe toxicity and high cost. Moreover, the emergence of drug resistance is a new limitation to successful patient outcomes. Therefore, the development of antifungals with novel targets is an essential strategy for the efficient management of infections. It is widely recognized that ion homeostasis is crucial for all living cells. Many studies have identified that ion-signaling and transduction networks are central to fungal survival by regulating gene expression, morphological transition, host invasion, stress response, and drug resistance. Dysregulation of ion homeostasis rapidly mediates cell death, forming the mechanistic basis of a growing number of compounds that elicit antifungal activity. Most of the potent antifungals have been widely used in the clinic, and certain of them have low toxicity, meaning that they may be expected to be used as antifungal drugs in the future. Hence, we briefly summarize the homeostasis regulation of several important ions, potential antifungal targets based on these ion-signaling networks, and antifungal compounds based on the disruption of ion homeostasis. This summary will help in designing effective drugs and identifying new targets for combating fungal diseases.
近几十年来,侵袭性真菌感染显著增加,导致免疫抑制患者的发病率和死亡率居高不下。()是人类最常见的机会性真菌病原体,可导致严重且常致命的血流感染。目前的抗真菌药物存在一些局限性,包括可用的抗真菌药物种类有限,某些药物毒性严重且成本高。此外,耐药性的出现是影响患者治疗效果的新限制因素。因此,开发具有新型靶点的抗真菌药物是有效管理真菌感染的重要策略。离子动态平衡对所有活细胞都至关重要,这一观点已得到广泛认可。许多研究表明,通过调节基因表达、形态转变、宿主侵袭、应激反应和耐药性,离子信号转导网络是真菌生存的核心。离子动态平衡的失调会迅速介导细胞死亡,这为越来越多的化合物发挥抗真菌活性提供了机制基础。大多数有效的抗真菌药物已广泛应用于临床,其中某些药物的毒性较低,因此有望在未来作为抗真菌药物使用。因此,我们简要总结了几种重要离子的动态平衡调节、基于这些离子信号网络的潜在抗真菌靶点,以及基于破坏离子动态平衡的抗真菌化合物。这一总结将有助于设计有效的药物和识别新的抗真菌靶点,以对抗真菌疾病。