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抗真菌耐药性、作为药物靶点的代谢途径及新型抗真菌药物:关于地方性双相真菌的概述

Antifungal Resistance, Metabolic Routes as Drug Targets, and New Antifungal Agents: An Overview about Endemic Dimorphic Fungi.

作者信息

Parente-Rocha Juliana Alves, Bailão Alexandre Melo, Amaral André Correa, Taborda Carlos Pelleschi, Paccez Juliano Domiraci, Borges Clayton Luiz, Pereira Maristela

机构信息

Departamento de Bioquímica e Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, GO, Brazil.

Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, GO, Brazil.

出版信息

Mediators Inflamm. 2017;2017:9870679. doi: 10.1155/2017/9870679. Epub 2017 Jun 13.

Abstract

Diseases caused by fungi can occur in healthy people, but immunocompromised patients are the major risk group for invasive fungal infections. Cases of fungal resistance and the difficulty of treatment make fungal infections a public health problem. This review explores mechanisms used by fungi to promote fungal resistance, such as the mutation or overexpression of drug targets, efflux and degradation systems, and pleiotropic drug responses. Alternative novel drug targets have been investigated; these include metabolic routes used by fungi during infection, such as trehalose and amino acid metabolism and mitochondrial proteins. An overview of new antifungal agents, including nanostructured antifungals, as well as of repositioning approaches is discussed. Studies focusing on the development of vaccines against antifungal diseases have increased in recent years, as these strategies can be applied in combination with antifungal therapy to prevent posttreatment sequelae. Studies focused on the development of a pan-fungal vaccine and antifungal drugs can improve the treatment of immunocompromised patients and reduce treatment costs.

摘要

真菌引起的疾病可发生在健康人身上,但免疫功能低下的患者是侵袭性真菌感染的主要风险群体。真菌耐药病例及治疗困难使真菌感染成为一个公共卫生问题。本综述探讨了真菌用于促进耐药性的机制,如药物靶点的突变或过表达、外排和降解系统以及多药耐药反应。已对替代性新药物靶点进行了研究;这些靶点包括真菌在感染期间使用的代谢途径,如海藻糖和氨基酸代谢以及线粒体蛋白。本文还讨论了新型抗真菌药物(包括纳米结构抗真菌药物)的概述以及重新定位方法。近年来,针对抗真菌疾病疫苗开发的研究有所增加,因为这些策略可与抗真菌治疗联合应用以预防治疗后后遗症。专注于开发泛真菌疫苗和抗真菌药物的研究可改善免疫功能低下患者的治疗并降低治疗成本。

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