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Transcriptome Profile of the Response of Paracoccidioides spp. to a Camphene Thiosemicarbazide Derivative.
PLoS One. 2015; 10(6):e0130703.Plos

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+Show Affiliations

Laboratório de Biologia Molecular, Instituto de Patologia Tropical e Saúde Pública Universidade Federal de Goiás, Goiânia, Brazil.Unidad de Biología Celular y Molecular, Corporación para Investigaciones Biológicas (CIB) and Facultad de Medicina Universidad de Antioquia, Medellín, Colombia.Laboratório de Biologia Molecular, Instituto de Patologia Tropical e Saúde Pública Universidade Federal de Goiás, Goiânia, Brazil.Laboratório de Produtos Naturais, Instituto de Química, Universidade Federal de Goiás, Goiânia, Brazil.Laboratório de Produtos Naturais, Instituto de Química, Universidade Federal de Goiás, Goiânia, Brazil.Laboratório de Fitoquímica e Síntese Orgânica, Departamento de Química, Universidade Estadual de Maringá, Paraná, Brazil.Laboratório de Fitoquímica e Síntese Orgânica, Departamento de Química, Universidade Estadual de Maringá, Paraná, Brazil.Laboratório de Biologia Molecular, Instituto de Patologia Tropical e Saúde Pública Universidade Federal de Goiás, Goiânia, Brazil.Laboratório de Biologia Molecular, Instituto de Patologia Tropical e Saúde Pública Universidade Federal de Goiás, Goiânia, Brazil.Laboratório de Biologia Molecular, Instituto de Patologia Tropical e Saúde Pública Universidade Federal de Goiás, Goiânia, Brazil.Unidad de Biología Celular y Molecular, Corporación para Investigaciones Biológicas (CIB) and Facultad de Medicina Universidad de Antioquia, Medellín, Colombia.Unidad de Biología Celular y Molecular, Corporación para Investigaciones Biológicas (CIB) and Facultad de Medicina Universidad de Antioquia, Medellín, Colombia.Laboratório de Biologia Molecular, Instituto de Patologia Tropical e Saúde Pública Universidade Federal de Goiás, Goiânia, Brazil.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26114868

Citation

do Carmo Silva, Lívia, et al. "Transcriptome Profile of the Response of Paracoccidioides Spp. to a Camphene Thiosemicarbazide Derivative." PloS One, vol. 10, no. 6, 2015, pp. e0130703.
do Carmo Silva L, Tamayo Ossa DP, Castro SV, et al. Transcriptome Profile of the Response of Paracoccidioides spp. to a Camphene Thiosemicarbazide Derivative. PLoS ONE. 2015;10(6):e0130703.
do Carmo Silva, L., Tamayo Ossa, D. P., Castro, S. V., Bringel Pires, L., Alves de Oliveira, C. M., Conceição da Silva, C., Coelho, N. P., Bailão, A. M., Parente-Rocha, J. A., Soares, C. M., Ruiz, O. H., Ochoa, J. G., & Pereira, M. (2015). Transcriptome Profile of the Response of Paracoccidioides spp. to a Camphene Thiosemicarbazide Derivative. PloS One, 10(6), e0130703. https://doi.org/10.1371/journal.pone.0130703
do Carmo Silva L, et al. Transcriptome Profile of the Response of Paracoccidioides Spp. to a Camphene Thiosemicarbazide Derivative. PLoS ONE. 2015;10(6):e0130703. PubMed PMID: 26114868.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transcriptome Profile of the Response of Paracoccidioides spp. to a Camphene Thiosemicarbazide Derivative. AU - do Carmo Silva,Lívia, AU - Tamayo Ossa,Diana Patrícia, AU - Castro,Symone Vitoriano da Conceição, AU - Bringel Pires,Ludmila, AU - Alves de Oliveira,Cecília Maria, AU - Conceição da Silva,Cleuza, AU - Coelho,Narcimário Pereira, AU - Bailão,Alexandre Melo, AU - Parente-Rocha,Juliana Alves, AU - Soares,Célia Maria de Almeida, AU - Ruiz,Orville Hernández, AU - Ochoa,Juan G McEwen, AU - Pereira,Maristela, Y1 - 2015/06/26/ PY - 2015/02/03/received PY - 2015/05/23/accepted PY - 2015/6/27/entrez PY - 2015/6/27/pubmed PY - 2016/4/12/medline SP - e0130703 EP - e0130703 JF - PloS one JO - PLoS ONE VL - 10 IS - 6 N2 - 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/26114868/Transcriptome_Profile_of_the_Response_of_Paracoccidioides_spp__to_a_Camphene_Thiosemicarbazide_Derivative_ L2 - http://dx.plos.org/10.1371/journal.pone.0130703 DB - PRIME DP - Unbound Medicine ER -