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Título : Transcriptome profile of the response of paracoccidioides spp. to a camphene thiosemicarbazide derivative
Autor : Do Carmo Silva, Lívia
Tamayo Ossa, Diana Patricia
Da Conceição Castro, Symone Vitoriano
Bringel Pires, Ludmila
Alves de Oliveira, Cecília Maria
Conceição da Silva, Cleuza
Pereira Coelho, Narcimário
Melo Bailão, Alexandre
Parente Rocha, Juliana Alves
De Almeida Soares, Célia Maria
Hernández Ruiz, Orville
McEwen Ochoa, Juan Guillermo
Pereira, Maristela
Palabras clave : Antifungal Agents
Antígenos Fúngicos
Fecha de publicación : 2015
Editorial : Public Library of Science
Citación : do Carmo Silva L, Tamayo Ossa DP, Castro SV, Bringel Pires L, Alves de Oliveira CM, Conceição da Silva C, Coelho NP, Bailão AM, Parente-Rocha JA, Soares CM, Ruiz OH, Ochoa JG, Pereira M. Transcriptome Profile of the Response of Paracoccidioides spp. to a Camphene Thiosemicarbazide Derivative. PLoS One. 2015 Jun 26;10(6):e0130703.
Resumen : 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.
URI : http://hdl.handle.net/10495/11579
ISSN : 19326203
Aparece en las colecciones: Instituto de Investigaciones Médicas

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