Parreira Vinícius da Silva Coutinho, Santos Letícia Graziela Costa, Rodrigues Marcio L, Passetti Fabio
Instituto Carlos Chagas, FIOCRUZ, Rua Prof. Algacyr Munhoz Mader, 3775, CEP 81350-010, Curitiba/PR, Brazil.
Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Brazil.
Comput Struct Biotechnol J. 2021 Apr 17;19:2286-2296. doi: 10.1016/j.csbj.2021.04.031. eCollection 2021.
Extracellular vesicles (EVs) are double-membrane particles associated with intercellular communication. Since the discovery of EV production in the fungus , the importance of EV release in its physiology and pathogenicity has been investigated. To date, few studies have investigated the proteomic content of EVs from multiple fungal species. Our main objective was to use an orthology approach to compare proteins identified by EV shotgun proteomics in 8 pathogenic and 1 nonpathogenic species. Using protein information from the UniProt and FungiDB databases, we integrated data for 11,433 hits in fungal EVs with an orthology perspective, resulting in 3,834 different orthologous groups. OG6_100083 (Hsp70 Pfam domain) was the unique orthologous group that was identified for all fungal species. Proteins with this protein domain are associated with the stress response, survival and morphological changes in different fungal species. Although no pathogenic orthologous group was found, we identified 5 orthologous groups exclusive to . Using the criteria of at least 7 pathogenic fungi to define a cluster, we detected the 4 unique pathogenic orthologous groups. Taken together, our data suggest that Hsp70-related proteins might play a key role in fungal EVs, regardless of the pathogenic status. Using an orthology approach, we identified at least 4 protein domains that could be novel therapeutic targets against pathogenic fungi. Our results were compiled in the herein described ExVe database, which is publicly available at http://exve.icc.fiocruz.br.
细胞外囊泡（EVs）是与细胞间通讯相关的双膜颗粒。自从在真菌中发现EV产生以来，人们已经研究了EV释放对其生理学和致病性的重要性。迄今为止，很少有研究调查多种真菌物种的EV蛋白质组内容。我们的主要目标是使用直系同源方法来比较通过EV鸟枪法蛋白质组学在8种致病真菌和1种非致病真菌中鉴定出的蛋白质。利用来自UniProt和FungiDB数据库的蛋白质信息，我们从直系同源的角度整合了真菌EV中11433个匹配的数据，得到了3834个不同的直系同源组。OG6_100083（Hsp70 Pfam结构域）是所有真菌物种都鉴定出的唯一直系同源组。具有该蛋白质结构域的蛋白质与不同真菌物种的应激反应、生存和形态变化相关。虽然没有发现致病直系同源组，但我们鉴定出了5个仅在……中的直系同源组。使用至少7种致病真菌的标准来定义一个聚类，我们检测到了4个独特的致病直系同源组。综上所述，我们的数据表明，无论致病状态如何，Hsp70相关蛋白可能在真菌EV中起关键作用。使用直系同源方法，我们鉴定出了至少4个可能成为抗致病真菌新治疗靶点的蛋白质结构域。我们的结果汇总在本文所述的ExVe数据库中，该数据库可在http://exve.icc.fiocruz.br上公开获取。
