title: Transcriptome Profile of the Response of Paracoccidioides spp. to a Camphene Thiosemicarbazide Derivative.
abstract: Paracoccidioidomycosis (PCM) is a systemic granulomatous human mycosis caused by fungi of the genus Paracoccidioides, which is geographically restricted to Latin America. Inhalation of spores, the infectious particles of the fungus, is a common route of infection. The PCM treatment of choice is azoles such as itraconazole, but sulfonamides and amphotericin B are used in some cases despite their toxicity to mammalian cells. The current availability of treatments highlights the need to identify and characterize novel targets for antifungal treatment of PCM as well as the need to search for new antifungal compounds obtained from natural sources or by chemical synthesis. To this end, we evaluated the antifungal activity of a camphene thiosemicarbazide derivative (TSC-C) compound on Paracoccidioides yeast. To determine the response of Paracoccidioides spp. to TSC-C, we analyzed the transcriptional profile of the fungus after 8 h of contact with the compound. The results demonstrate that Paracoccidioides lutzii induced the expression of genes related to metabolism; cell cycle and DNA processing; biogenesis of cellular components; cell transduction/signal; cell rescue, defense and virulence; cellular transport, transport facilities and transport routes; energy; protein synthesis; protein fate; transcription; and other proteins without classification. Additionally, we observed intensely inhibited genes related to protein synthesis. Analysis by fluorescence microscopy and flow cytometry revealed that the compound induced the production of reactive oxygen species. Using an isolate with down-regulated SOD1 gene expression (SOD1-aRNA), we sought to determine the function of this gene in the defense of Paracoccidioides yeast cells against the compound. Mutant cells were more susceptible to TSC-C, demonstrating the importance of this gene in response to the compound. The results presented herein suggest that TSC-C is a promising candidate for PCM treatment.
authors.affiliation: Laboratório de Biologia Molecular, Instituto de Patologia Tropical e Saúde Pública Universidade Federal de Goiás, Goiânia, Brazil.
authors.forename: Lívia
authors.initials: L
authors.lastname: do Carmo Silva
authors.affiliation: Unidad de Biología Celular y Molecular, Corporación para Investigaciones Biológicas (CIB) and Facultad de Medicina Universidad de Antioquia, Medellín, Colombia.
authors.forename: Diana Patrícia
authors.initials: DP
authors.lastname: Tamayo Ossa
authors.affiliation: Laboratório de Biologia Molecular, Instituto de Patologia Tropical e Saúde Pública Universidade Federal de Goiás, Goiânia, Brazil.
authors.forename: Symone Vitoriano da Conceição
authors.initials: SV
authors.lastname: Castro
authors.affiliation: Laboratório de Produtos Naturais, Instituto de Química, Universidade Federal de Goiás, Goiânia, Brazil.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Bringel Pires
authors.affiliation: Laboratório de Produtos Naturais, Instituto de Química, Universidade Federal de Goiás, Goiânia, Brazil.
authors.forename: Cecília Maria
authors.initials: CM
authors.lastname: Alves de Oliveira
authors.affiliation: Laboratório de Fitoquímica e Síntese Orgânica, Departamento de Química, Universidade Estadual de Maringá, Paraná, Brazil.
authors.forename: Cleuza
authors.initials: C
authors.lastname: Conceição da Silva
authors.affiliation: Laboratório de Fitoquímica e Síntese Orgânica, Departamento de Química, Universidade Estadual de Maringá, Paraná, Brazil.
authors.forename: Narcimário Pereira
authors.initials: NP
authors.lastname: Coelho
authors.affiliation: Laboratório de Biologia Molecular, Instituto de Patologia Tropical e Saúde Pública Universidade Federal de Goiás, Goiânia, Brazil.
authors.forename: Alexandre Melo
authors.initials: AM
authors.lastname: Bailão
authors.affiliation: Laboratório de Biologia Molecular, Instituto de Patologia Tropical e Saúde Pública Universidade Federal de Goiás, Goiânia, Brazil.
authors.forename: Juliana Alves
authors.initials: JA
authors.lastname: Parente-Rocha
authors.affiliation: Laboratório de Biologia Molecular, Instituto de Patologia Tropical e Saúde Pública Universidade Federal de Goiás, Goiânia, Brazil.
authors.forename: Célia Maria de Almeida
authors.initials: CM
authors.lastname: Soares
authors.affiliation: Unidad de Biología Celular y Molecular, Corporación para Investigaciones Biológicas (CIB) and Facultad de Medicina Universidad de Antioquia, Medellín, Colombia.
authors.forename: Orville Hernández
authors.initials: OH
authors.lastname: Ruiz
authors.affiliation: Unidad de Biología Celular y Molecular, Corporación para Investigaciones Biológicas (CIB) and Facultad de Medicina Universidad de Antioquia, Medellín, Colombia.
authors.forename: Juan G McEwen
authors.initials: JG
authors.lastname: Ochoa
authors.affiliation: Laboratório de Biologia Molecular, Instituto de Patologia Tropical e Saúde Pública Universidade Federal de Goiás, Goiânia, Brazil.
authors.forename: Maristela
authors.initials: M
authors.lastname: Pereira
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D000081008:Bicyclic Monoterpenes; D020224:Expressed Sequence Tags; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects / Q000235:genetics; D010228:Paracoccidioides / Q000187:drug effects / Q000235:genetics*; D012663:Semicarbazides / Q000737:chemistry*; D013729:Terpenes / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D000081008:Bicyclic Monoterpenes; D012663:Semicarbazides; D013729:Terpenes; C005151:thiosemicarbazide; C019286:camphene