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Transcriptional profile of Paracoccidioides spp. in response to itraconazole
BACKGROUND: Itraconazole is currently used to treat paracoccidioidomycosis. The mechanism of action of azoles has been elucidated in some fungi, although little is known regarding its mechanism of action in Paracoccidioides spp. The present work focused on identification of regulated transcripts usi...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3975141/ https://www.ncbi.nlm.nih.gov/pubmed/24690401 http://dx.doi.org/10.1186/1471-2164-15-254 |
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author | Neto, Benedito Rodrigues da Silva Carvalho, Patrícia Fernanda Zambuzzi Bailão, Alexandre Melo Martins, Wellington Santos de Almeida Soares, Célia Maria Pereira, Maristela |
author_facet | Neto, Benedito Rodrigues da Silva Carvalho, Patrícia Fernanda Zambuzzi Bailão, Alexandre Melo Martins, Wellington Santos de Almeida Soares, Célia Maria Pereira, Maristela |
author_sort | Neto, Benedito Rodrigues da Silva |
collection | PubMed |
description | BACKGROUND: Itraconazole is currently used to treat paracoccidioidomycosis. The mechanism of action of azoles has been elucidated in some fungi, although little is known regarding its mechanism of action in Paracoccidioides spp. The present work focused on identification of regulated transcripts using representational difference analysis of Paracoccidioides spp. yeast cells treated with itraconazole for 1 and 2 h. RESULTS: Paracoccidioides Pb01 genes up-regulated by itraconazole included genes involved in cellular transport, metabolism/energy, transcription, cell rescue, defense and virulence. ERG11, ERG6, ERG3, ERG5 and ERG25 were up-regulated at multiple time points. In vivo infection experiments in mice corroborated the in vitro results. Ergosterol levels and distribution were evaluated in Paracoccidioides Pb18 yeast cells, and the results demonstrate that both factors were changed in the fungus treated with itraconazole. CONCLUSION: To our knowledge, this is the first transcriptional analysis of Paracoccidioides spp. exposed to a triazole drug. Here acetyl seems to be intensively produced from different metabolic pathways to produce ergosterol by the action of ergosterol synthesis related enzymes, which were also affected in other fungi. Among the genes affected, we identified genes in common with other fungi, as well as genes unique to Paracoccidioides Pb01. Those genes could be considered target to new drugs. Voltage-gated Ca(2+) alpha subunit (CAV), Tetracycline resistance protein (TETA) and Hemolisyn-iii channel protein (HLYiii) were found only here and a probably involvement with resistence to itraconazole could be investigated in the future. However our findings do not permit inference to current clinical practice. |
format | Online Article Text |
id | pubmed-3975141 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-39751412014-04-05 Transcriptional profile of Paracoccidioides spp. in response to itraconazole Neto, Benedito Rodrigues da Silva Carvalho, Patrícia Fernanda Zambuzzi Bailão, Alexandre Melo Martins, Wellington Santos de Almeida Soares, Célia Maria Pereira, Maristela BMC Genomics Research Article BACKGROUND: Itraconazole is currently used to treat paracoccidioidomycosis. The mechanism of action of azoles has been elucidated in some fungi, although little is known regarding its mechanism of action in Paracoccidioides spp. The present work focused on identification of regulated transcripts using representational difference analysis of Paracoccidioides spp. yeast cells treated with itraconazole for 1 and 2 h. RESULTS: Paracoccidioides Pb01 genes up-regulated by itraconazole included genes involved in cellular transport, metabolism/energy, transcription, cell rescue, defense and virulence. ERG11, ERG6, ERG3, ERG5 and ERG25 were up-regulated at multiple time points. In vivo infection experiments in mice corroborated the in vitro results. Ergosterol levels and distribution were evaluated in Paracoccidioides Pb18 yeast cells, and the results demonstrate that both factors were changed in the fungus treated with itraconazole. CONCLUSION: To our knowledge, this is the first transcriptional analysis of Paracoccidioides spp. exposed to a triazole drug. Here acetyl seems to be intensively produced from different metabolic pathways to produce ergosterol by the action of ergosterol synthesis related enzymes, which were also affected in other fungi. Among the genes affected, we identified genes in common with other fungi, as well as genes unique to Paracoccidioides Pb01. Those genes could be considered target to new drugs. Voltage-gated Ca(2+) alpha subunit (CAV), Tetracycline resistance protein (TETA) and Hemolisyn-iii channel protein (HLYiii) were found only here and a probably involvement with resistence to itraconazole could be investigated in the future. However our findings do not permit inference to current clinical practice. BioMed Central 2014-04-01 /pmc/articles/PMC3975141/ /pubmed/24690401 http://dx.doi.org/10.1186/1471-2164-15-254 Text en Copyright © 2014 Neto et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. |
spellingShingle | Research Article Neto, Benedito Rodrigues da Silva Carvalho, Patrícia Fernanda Zambuzzi Bailão, Alexandre Melo Martins, Wellington Santos de Almeida Soares, Célia Maria Pereira, Maristela Transcriptional profile of Paracoccidioides spp. in response to itraconazole |
title | Transcriptional profile of Paracoccidioides spp. in response to itraconazole |
title_full | Transcriptional profile of Paracoccidioides spp. in response to itraconazole |
title_fullStr | Transcriptional profile of Paracoccidioides spp. in response to itraconazole |
title_full_unstemmed | Transcriptional profile of Paracoccidioides spp. in response to itraconazole |
title_short | Transcriptional profile of Paracoccidioides spp. in response to itraconazole |
title_sort | transcriptional profile of paracoccidioides spp. in response to itraconazole |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3975141/ https://www.ncbi.nlm.nih.gov/pubmed/24690401 http://dx.doi.org/10.1186/1471-2164-15-254 |
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