MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology , Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing 100730 , China.
J Proteome Res. 2018 Apr 6;17(4):1436-1451. doi: 10.1021/acs.jproteome.7b00793. Epub 2018 Mar 28.
Trichophyton rubrum is the most common fungal pathogen in the world, which has been studied as an important dermatophyte model organism. Despite the prevalence of T. rubrum, the available antifungal therapies are not sufficiently efficient. In this study, we performed the first comparison between the two major growth stages of T. rubrum: conidial and mycelial stages, based on their whole-cell proteomes and lysine acetylomes. In total, 4343 proteins were identified in both stages, and 1879 proteins were identified as differentially expressed between the two stages. The results showed that secretory proteases were more abundant in conidia, while aerobic metabolism and protein synthesis were significantly activated in the mycelial stage. In addition, 386 acetylated sites on 285 proteins and 5414 acetylated sites on 2335 proteins were identified in conidia and mycelia, respectively. The acetylation modifications were highly involved in metabolism and protein synthesis in both stages but differentially involved in Kyoto Encyclopedia of Genes and Genomes pathways and in epigenetic regulation between the two stages. Furthermore, inhibition of acetyltransferases or deacetylases significantly inhibited fungal growth and induced apoptosis. These results will enhance our understanding of the biological and physiological characteristics of T. rubrum and facilitate the development of improved therapies targeting these medically important pathogenic fungi.
红色毛癣菌是世界上最常见的真菌病原体，已被研究作为一种重要的皮肤真菌模式生物。尽管红色毛癣菌普遍存在，但现有的抗真菌疗法效率不够高。在这项研究中，我们首次对红色毛癣菌的两个主要生长阶段——分生孢子和菌丝阶段进行了比较，基于它们的全细胞蛋白质组和赖氨酸乙酰化组。在这两个阶段共鉴定出 4343 种蛋白质，其中 1879 种被鉴定为在两个阶段之间差异表达。结果表明，分泌蛋白酶在分生孢子中更为丰富，而有氧代谢和蛋白质合成在菌丝阶段显著激活。此外，在分生孢子和菌丝中分别鉴定出 386 个和 5414 个乙酰化位点，分别位于 285 种和 2335 种蛋白质上。乙酰化修饰在两个阶段的代谢和蛋白质合成中都高度参与，但在京都基因与基因组百科全书通路和两个阶段的表观遗传调控中差异参与。此外，乙酰转移酶或去乙酰化酶的抑制显著抑制了真菌的生长并诱导了细胞凋亡。这些结果将增强我们对红色毛癣菌生物学和生理学特征的理解，并有助于开发针对这些具有医学重要性的致病真菌的改良疗法。
