title: Peroxide sensing and signaling in the Sporothrix schenckii complex: an in silico analysis to uncover putative mechanisms regulating the Hog1 and AP-1 like signaling pathways.
abstract: In order to understand how fungal pathogens can survive inside the host, we must analyze how they evade the fungicidal mechanisms mounted by the host's immune system, such as generation of toxic reactive oxygen species. Studies have shown that infections caused by Sporothrix brasiliensis can be more aggressive than those due to Sporothrix schenckii. Therefore, we propose to analyze and compare the ability of these two pathogenic species to counteract oxidative stress, which, as noted, can be relevant in the host response to infection. We have shown that S. brasiliensis is more resistant to different oxidants, such as H2O2 and menadione, when compared with S. schenckii. Furthermore, our results suggest that the molecular mechanisms by which Sporothrix spp. AP-1 like transcription factors are regulated probably differs from the one seen in other fungal pathogens. Interestingly, comparison between sequences of SbHog1 and SsHog1 stress activated protein kinases suggest that S. brasiliensis Hog1 display mutations that could account for the differences seen in stress sensitivities of these two species. In summary, this is the first study to our knowledge to investigate oxidative stress responses of Sporothrix spp. and provided a model that can be employed in vivo to address how these fungal pathogens can surmount the oxidative stress generated by the host.
authors.affiliation: Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Ivy
authors.initials: I
authors.lastname: Ortega
authors.affiliation: Department of Cell Biology, Universidade de Brasília, Brasília, DF, Brazil.
authors.forename: Maria Sueli
authors.initials: MS
authors.lastname: Soares Felipe
authors.affiliation: Laboratório Nacional de Computação Científica, Petrópolis, RJ, Brazil.
authors.forename: Ana Tereza Ribeiro
authors.initials: AT
authors.lastname: Vasconcelos
authors.affiliation: Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Leila Maria
authors.initials: LM
authors.lastname: Lopes Bezerra
authors.affiliation: Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil alesdantas@gmail.com.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Da Silva Dantas
mesh_terms: D019295:Computational Biology; D015966:Gene Expression Regulation, Fungal; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D020125:Mutation, Missense; D018384:Oxidative Stress; D010545:Peroxides / Q000633:toxicity*; D015398:Signal Transduction; D013175:Sporothrix / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D013312:Stress, Physiological; D018808:Transcription Factor AP-1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D010545:Peroxides; D018808:Transcription Factor AP-1; D020928:Mitogen-Activated Protein Kinases
keywords: AP-1 like transcription factor; Hog1 stress activated protein kinase; oxidative stress; signaling; sporotrichosis