Lutzii副球菌真菌是副球菌属的一种,负责被忽视的人类真菌病,拉丁美洲特有的,副角菌病(PCM)。为了在宿主中生存,在感染过程中,真菌在低水平的氧气(缺氧)下克服了恶劣的环境。缺氧适应机制在人类病原真菌之间是可变的,值得在副甲虫属中进行研究。先前的蛋白质组学结果鉴定了路氏疟原虫对缺氧有反应,并且它具有SrbA转录因子的功能同源物,一个很好描述的低氧调节剂。然而,SrbA对基因的直接调控及其在进行蛋白质相互作用时控制的生物学过程尚未揭示。这项研究的目的是证明SrbA靶基因在布鲁兹疟原虫中的潜力。此外,显示SrbA三维方面以及蛋白质相互作用图和与预测靶标相互作用的重要区域。结果表明,SrbA调控的基因涉及多个生物学类别,比如新陈代谢,能源,细胞维持的基础过程,真菌形态发生,防御,毒力,和信号转导。此外,为了研究SrbA作为蛋白质的作用,我们进行了3D模拟以及与该低氧调节因子相关的蛋白质-蛋白质网络.这些计算机分析揭示了与这种面临缺氧的病原体生物学有关的相关方面,并强调了SrbA作为未来抗真菌靶标的潜力。
The fungus Paracoccidioides lutzii is one of the species of the Paracoccidioides genus, responsible for a neglected human mycosis, endemic in Latin America, the paracoccidioidomycosis (PCM). In order to survive in the host, the fungus overcomes a hostile environment under low levels of oxygen (hypoxia) during the infectious process. The hypoxia adaptation mechanisms are variable among human pathogenic fungi and worthy to be investigated in Paracoccidoides spp. Previous proteomic results identified that P. lutzii responds to hypoxia and it has a functional homolog of the SrbA transcription factor, a well-described hypoxic regulator. However, the direct regulation of genes by SrbA and the biological processes it governs while performing protein interactions have not been revealed yet. The goal of this study was to demonstrate the potential of SrbA targets genes in P. lutzii. In addition, to show the SrbA three-dimensional aspects as well as a protein interaction map and important regions of interaction with predicted targets. The results show that SrbA-regulated genes were involved with several biological categories, such as metabolism, energy, basal processes for cell maintenance, fungal morphogenesis, defense, virulence, and signal transduction. Moreover, in order to investigate the SrbA\'s role as a protein, we performed a 3D simulation and also a protein-protein network linked to this hypoxic regulator. These in silico analyses revealed relevant aspects regarding the biology of this pathogen facing hypoxia and highlight the potential of SrbA as an antifungal target in the future.