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念珠菌属中的毒力因子。

Virulence Factors in Candida species.

机构信息

Faculty of Chemistry, Warsaw University of Technology, 00-664 Warsaw, Poland.

出版信息

Curr Protein Pept Sci. 2020;21(3):313-323. doi: 10.2174/1389203720666190722152415.

Abstract

Fungal diseases are severe and have very high morbidity as well as up to 60% mortality for patients diagnosed with invasive fungal infection. In this review, in vitro and in vivo studies provided us with the insight into the role of Candida virulence factors that mediate their success as pathogens, such as: membrane and cell wall (CW) barriers, dimorphism, biofilm formation, signal transduction pathway, proteins related to stress tolerance, hydrolytic enzymes (e.g. proteases, lipases, haemolysins), and toxin production. The review characterized the virulence of clinically important C. albicans, C. parapsilosis, C. tropicalis, C. glabrata and C. krusei. Due to the white-opaque transition in the mating-type locus MTL-homozygous cells, C. albicans demonstrates an advantage over other less related species of Candida as a human commensal and pathogen. It was reviewed that Candida ergosterol biosynthesis genes play a role in cellular stress and are essential for Candida pathogenesis both in invasive and superficial infections. Hydrolases associated with CW are involved in the host-pathogen interactions. Adhesins are crucial in colonization and biofilm formation, an important virulence factor for candidiasis. Calcineurin is involved in membrane and CW stress as well as virulence. The hyphae-specific toxin, named candidalysin, invades mucosal cells facilitating fungal invasion into deeper tissues. Expression of this protein promotes resistance to neutrophil killing in candidiasis. The virulence factors provide immunostimulatory factors, activating dendric cells and promoting T cell infiltration and activation. Targeting virulence factors, can reduce the risk of resistance development in Candida infections.

摘要

真菌感染严重,发病率极高,侵袭性真菌感染患者的死亡率高达 60%。在这篇综述中,体外和体内研究使我们深入了解了白色念珠菌、近平滑念珠菌、热带念珠菌、光滑念珠菌和克柔念珠菌等致病真菌的毒力因子在介导其成功致病过程中的作用,这些毒力因子包括:膜和细胞壁(CW)屏障、二态性、生物膜形成、信号转导途径、与应激耐受相关的蛋白质、水解酶(如蛋白酶、脂肪酶、溶菌酶)和毒素产生。本综述描述了临床上重要的白色念珠菌、近平滑念珠菌、热带念珠菌、光滑念珠菌和克柔念珠菌的毒力特征。由于交配型位点 MTL 纯合细胞中的白-暗转换,白色念珠菌在作为人类共生菌和病原体方面比其他亲缘关系较远的念珠菌具有优势。综述认为,真菌麦角固醇生物合成基因在细胞应激中发挥作用,对于侵袭性和浅表性感染中的真菌发病机制都是必不可少的。与 CW 相关的水解酶参与宿主-病原体相互作用。黏附素在定植和生物膜形成中起关键作用,是念珠菌病的重要毒力因子。钙调神经磷酸酶参与膜和 CW 应激以及毒力。菌丝特异性毒素,命名为念珠菌溶素,可入侵黏膜细胞,促进真菌向更深层组织侵袭。该蛋白的表达促进了念珠菌病中中性粒细胞杀伤的耐药性。毒力因子提供免疫刺激因子,激活树突状细胞,促进 T 细胞浸润和激活。针对毒力因子,可以降低念珠菌感染中耐药发展的风险。

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