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巴西副球孢子菌的毒力因子作为治疗靶点:综述。

Virulence factors of Paracoccidioides brasiliensis as therapeutic targets: a review.

机构信息

Universidade Federal de Alfenas, Alfenas, Brazil.

出版信息

Antonie Van Leeuwenhoek. 2020 May;113(5):593-604. doi: 10.1007/s10482-019-01382-5. Epub 2020 Jan 4.

Abstract

Paracoccidiodomycosis (PCM) is a systemic mycosis caused by the fungus Paracoccidioides brasiliensis and Paracoccidioides lutzii. The disease requires long and complicated treatment. The aim of this review is to address the fungal virulence factors that could be the target of the development of new drugs for PCM treatment. Virulence factors favoring the process of fungal infection and pathogenicity are considered as a microbial attribute associated with host susceptibility. P. brasiliensis has some known virulence factors which are 43 kDa glycoprotein (gp 43) which is an important fungal antigen, 70 kDa glycoprotein (gp 70), the carbohydrates constituting the fungal cell wall α-1,3, glucan and β-1,3-glucan, cell adhesion molecules and the presence of melanin pigments. The discovery and development of drugs that interact with these factors, such as inhibitors of β-1,3-glucan, reduced synthesis of gp 43, inhibitors of melanin production, is of great importance for the treatment of PCM. The study of virulence factors favors the understanding of pathogen-host relationships, aiming to evaluate the possibility of developing new therapeutic targets and mechanisms that these molecules play in the infectious process, favoring the design of a more specific treatment for this disease.

摘要

球孢子菌病(PCM)是一种由巴西副球孢子菌和秘鲁副球孢子菌引起的系统性真菌病。该疾病需要长期而复杂的治疗。本综述旨在探讨真菌毒力因子,这些因子可能成为治疗 PCM 的新药开发的靶点。有利于真菌感染和致病性过程的毒力因子被认为是与宿主易感性相关的微生物属性。巴西副球孢子菌有一些已知的毒力因子,如 43 kDa 糖蛋白(gp 43),这是一种重要的真菌抗原,70 kDa 糖蛋白(gp 70),构成真菌细胞壁的碳水化合物α-1,3-葡聚糖和β-1,3-葡聚糖,细胞黏附分子和黑色素的存在。发现和开发与这些因子相互作用的药物,如β-1,3-葡聚糖抑制剂、gp 43 合成减少剂、黑色素生成抑制剂,对于治疗 PCM 非常重要。毒力因子的研究有助于理解病原体-宿主的关系,旨在评估开发新的治疗靶点和机制的可能性,这些分子在感染过程中发挥作用,有利于为这种疾病设计更具特异性的治疗方法。

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