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.

真菌Paracoccidioides lutzii 是 Paracoccidioides 属的物种之一，是导致拉丁美洲流行的一种被忽视的人类真菌病，即副球孢子菌病 (PCM) 的原因。为了在宿主中生存，真菌在感染过程中克服了低氧（缺氧）下的恶劣环境。人类病原真菌的缺氧适应机制各不相同，值得在副球孢子菌中进行研究。先前的蛋白质组学结果确定P. lutzii对缺氧有反应，并且它具有 SrbA 转录因子的功能同源物，这是一种充分描述的缺氧调节剂。然而，尚未揭示 SrbA 对基因的直接调节及其在进行蛋白质相互作用时所控制的生物学过程。本研究的目的是证明 SrbA 靶基因在P. lutzii 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目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，例如代谢、能量、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 模拟以及与这种缺氧调节剂相关的蛋白质-蛋白质网络。这些计算机分析揭示了这种病原体面临缺氧的生物学相关方面，并突出了 SrbA 作为未来抗真菌靶点的潜力。