The dual role of SrbA from Paracoccidioides lutzii: a hypoxic regulator.

Abstract

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.