Amity Institute of Integrative Science and Health and Amity Institute of Biotechnology, Amity University Haryana, Gurgaon, Haryana, India.
Amity Institute of Integrative Science and Health and Amity Institute of Biotechnology, Amity University Haryana, Gurgaon, Haryana, India.
Fungal Genet Biol. 2019 Nov;132:103252. doi: 10.1016/j.fgb.2019.103252. Epub 2019 Jul 11.
Over-expression of the human P-glycoprotein (P-gp) in tumor cells is a classic example of an ABC protein serving as a hindrance to effective chemotherapy. The existence of proteins homologous to P-gp in organisms encompassing the entire living kingdom highlights extrusion of drugs as a general mechanism of multidrug resistance. Infections caused by opportunistic human fungal pathogens such as Candida species are very common and has intensified in recent years. The typical hosts, who possess suppressed immune systems due to conditions such as HIV and transplantation surgery etc., are prone to fungal infections. Prolonged chemotherapy induces fungal cells to eventually develop tolerance to most of the antifungals currently in clinical use. Amongst other prominent mechanisms of antifungal resistance such as manipulation of the drug target, rapid efflux achieved through overexpression of multidrug transporters has emerged as a major resistance mechanism for azoles. Herein, the azole-resistant clinical isolates of Candida species utilize a few select efflux pump proteins belonging to the ABC and MFS superfamilies, to deter the toxic accumulation of therapeutic azoles and thus, facilitating cell survival. In this article, we summarize and discuss the clinically relevant mechanisms of azole resistance in Candida albicans and non-albicans Candida (NAC) species, specifically highlighting the role of multidrug efflux proteins in the phenomenon.
人 P-糖蛋白（P-gp）在肿瘤细胞中的过度表达是 ABC 蛋白作为有效化疗障碍的经典范例。在包括整个生命王国的生物体中存在与 P-gp 同源的蛋白质，突出了药物外排是多药耐药的一般机制。机会性人类真菌病原体（如念珠菌属）引起的感染非常普遍，近年来有所加剧。由于 HIV 和移植手术等原因而免疫系统受到抑制的典型宿主容易发生真菌感染。长期化疗导致真菌细胞最终对目前临床使用的大多数抗真菌药物产生耐药性。在其他突出的抗真菌耐药机制中，如药物靶标的操纵，通过过度表达多药转运蛋白实现的快速外排已成为唑类药物的主要耐药机制。在此，念珠菌属的唑类耐药临床分离株利用少数几种属于 ABC 和 MFS 超家族的选择性外排泵蛋白，阻止治疗性唑类药物的毒性积累，从而促进细胞存活。在本文中，我们总结和讨论了白色念珠菌和非白色念珠菌（NAC）种属中唑类耐药的临床相关机制，特别强调了多药外排蛋白在这一现象中的作用。
