PMID- 26114868 OWN - NLM STAT- MEDLINE DCOM- 20160411 LR - 20191210 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 10 IP - 6 DP - 2015 TI - Transcriptome Profile of the Response of Paracoccidioides spp. to a Camphene Thiosemicarbazide Derivative. PG - e0130703 LID - 10.1371/journal.pone.0130703 [doi] LID - e0130703 AB - 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. FAU - do Carmo Silva, Livia AU - do Carmo Silva L AD - Laboratorio de Biologia Molecular, Instituto de Patologia Tropical e Saude Publica Universidade Federal de Goias, Goiania, Brazil. FAU - Tamayo Ossa, Diana Patricia AU - Tamayo Ossa DP AD - Unidad de Biologia Celular y Molecular, Corporacion para Investigaciones Biologicas (CIB) and Facultad de Medicina Universidad de Antioquia, Medellin, Colombia. FAU - Castro, Symone Vitoriano da Conceicao AU - Castro SV AD - Laboratorio de Biologia Molecular, Instituto de Patologia Tropical e Saude Publica Universidade Federal de Goias, Goiania, Brazil. FAU - Bringel Pires, Ludmila AU - Bringel Pires L AD - Laboratorio de Produtos Naturais, Instituto de Quimica, Universidade Federal de Goias, Goiania, Brazil. FAU - Alves de Oliveira, Cecilia Maria AU - Alves de Oliveira CM AD - Laboratorio de Produtos Naturais, Instituto de Quimica, Universidade Federal de Goias, Goiania, Brazil. FAU - Conceicao da Silva, Cleuza AU - Conceicao da Silva C AD - Laboratorio de Fitoquimica e Sintese Organica, Departamento de Quimica, Universidade Estadual de Maringa, Parana, Brazil. FAU - Coelho, Narcimario Pereira AU - Coelho NP AD - Laboratorio de Fitoquimica e Sintese Organica, Departamento de Quimica, Universidade Estadual de Maringa, Parana, Brazil. FAU - Bailao, Alexandre Melo AU - Bailao AM AD - Laboratorio de Biologia Molecular, Instituto de Patologia Tropical e Saude Publica Universidade Federal de Goias, Goiania, Brazil. FAU - Parente-Rocha, Juliana Alves AU - Parente-Rocha JA AD - Laboratorio de Biologia Molecular, Instituto de Patologia Tropical e Saude Publica Universidade Federal de Goias, Goiania, Brazil. FAU - Soares, Celia Maria de Almeida AU - Soares CM AD - Laboratorio de Biologia Molecular, Instituto de Patologia Tropical e Saude Publica Universidade Federal de Goias, Goiania, Brazil. FAU - Ruiz, Orville Hernandez AU - Ruiz OH AD - Unidad de Biologia Celular y Molecular, Corporacion para Investigaciones Biologicas (CIB) and Facultad de Medicina Universidad de Antioquia, Medellin, Colombia. FAU - Ochoa, Juan G McEwen AU - Ochoa JG AD - Unidad de Biologia Celular y Molecular, Corporacion para Investigaciones Biologicas (CIB) and Facultad de Medicina Universidad de Antioquia, Medellin, Colombia. FAU - Pereira, Maristela AU - Pereira M AD - Laboratorio de Biologia Molecular, Instituto de Patologia Tropical e Saude Publica Universidade Federal de Goias, Goiania, Brazil. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150626 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Antifungal Agents) RN - 0 (Bicyclic Monoterpenes) RN - 0 (Semicarbazides) RN - 0 (Terpenes) RN - 6056O8W6ET (thiosemicarbazide) RN - G3VG94Z26E (camphene) SB - IM MH - Antifungal Agents/chemistry/*pharmacology MH - Bicyclic Monoterpenes MH - Expressed Sequence Tags MH - Gene Expression Regulation, Fungal/drug effects/genetics MH - Paracoccidioides/drug effects/*genetics MH - Semicarbazides/*chemistry MH - Terpenes/*chemistry/*pharmacology PMC - PMC4483234 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2015/06/27 06:00 MHDA- 2016/04/12 06:00 PMCR- 2015/06/26 CRDT- 2015/06/27 06:00 PHST- 2015/02/03 00:00 [received] PHST- 2015/05/23 00:00 [accepted] PHST- 2015/06/27 06:00 [entrez] PHST- 2015/06/27 06:00 [pubmed] PHST- 2016/04/12 06:00 [medline] PHST- 2015/06/26 00:00 [pmc-release] AID - PONE-D-14-52126 [pii] AID - 10.1371/journal.pone.0130703 [doi] PST - epublish SO - PLoS One. 2015 Jun 26;10(6):e0130703. doi: 10.1371/journal.pone.0130703. eCollection 2015.