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

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 (hypox...

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Bibliographic Details
Published in:	Brazilian journal of microbiology Vol. 52; no. 3; pp. 1135 - 1149
Main Authors:	de Sousa, Lorena Ordones, Oliveira, Lucas Nojosa, Naves, Raphaela Barbosa, Pereira, André Luiz Araújo, Santiago Freitas e Silva, Kleber, de Almeida Soares, Célia Maria, de Sousa Lima, Patrícia
Format:	Journal Article
Language:	English
Published:	Cham Springer International Publishing 01-09-2021 Springer Nature B.V
Subjects:	Bacterial Bacterial, Fungal and Virus Molecular Biology - Research Paper Biological activity Biomedical and Life Sciences Energy metabolism Food Microbiology Fungal and Virus Molecular Biology - Research Paper Fungal Proteins - genetics Fungi Fungicides Gene regulation Genes Homology Humans Hypoxia Life Sciences Medical Microbiology Microbial Ecology Microbial Genetics and Genomics Microbiology Morphogenesis Mycology Mycosis Paracoccidioides - genetics Paracoccidioides lutzii Paracoccidioidomycosis Protein interaction Proteins Proteomics Signal processing Signal transduction South American blastomycosis Virulence Hypoxia Three-dimensional structure SrbA-regulated genes Protein-protein interactions P. lutzii
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Responsible Editor: Rosana Puccia
ISSN:	1517-8382 1678-4405
DOI:	10.1007/s42770-021-00527-x