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Transcriptome analysis of Aspergillus fumigatus exposed to voriconazole

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Abstract

For a comprehensive evaluation of genes that have their expression modulated during exposure of the mycelia to voriconazole, we performed a large-scale analysis of gene expression in Aspergillus fumigatus using a microarray hybridization approach. By comparing the expression of genes between the reference time and after addition of voriconazole (30, 60, 120, and 240 min), we identified 2,271 genes differentially expressed in the wild-type strain. To validate the expression of some of these genes during exposure to voriconazole, we analyzed 13 genes showing higher expression in the presence of voriconazole by real-time RT-PCR. Although the magnitudes of induction differed between the two experimental systems, in about 85% of the cases they were in good agreement with the microarray data. To our knowledge this is the first study of microarray hybridization analysis for a filamentous fungus exposed to an antifungal agent. In our study, we have observed: (i) a decreased mRNA expression of various ergosterol biosynthesis genes; (ii) increased mRNA levels of genes involved in a variety of cell functions, such as transporters, transcription factors, proteins involved in cell metabolism, and hypothetical proteins; and (iii) the involvement of the cyclic AMP-protein kinase signaling pathway in the increased mRNA expression of several of these genes.

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Acknowledgments

We would like to thank the Fundação de Amparo a Pesquisa do Estado de São Paulo and Conselho Nacional de Desenvolvimento Científico e Tecnológico, both from Brazil, for financial support for our research, and SPP1160 of the Deutsche Forschungsgemeinschaft for A.A.B. Microarray analysis work was supported by NIAID grant to W.C.N. We also thank the two anonymous reviewers and the editor for the suggestions.

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Authors and Affiliations

  1. Departamento de Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café S/N , CEP 14040-903, Ribeirão Preto, São Paulo, Brazil

    Márcia Eliana da Silva Ferreira, Iran Malavazi, Marcela Savoldi & Gustavo H. Goldman

  2. Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research, Infection Biology-HansKnoell Institute (HKI), University of Jena, Jena, Germany

    Axel A. Brakhage

  3. Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil

    Maria Helena S. Goldman

  4. The Institute for Genomic Research, Rockville, MD, 20850, USA

    H. Stanley Kim & William C. Nierman

  5. Department of Biochemistry and Molecular Biology, The George Washington University School of Medicine, Washington, DC, 20037, USA

    H. Stanley Kim & William C. Nierman

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  1. Márcia Eliana da Silva Ferreira
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  2. Iran Malavazi
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  3. Marcela Savoldi
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  4. Axel A. Brakhage
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  5. Maria Helena S. Goldman
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  6. H. Stanley Kim
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  7. William C. Nierman
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  8. Gustavo H. Goldman
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Correspondence to Gustavo H. Goldman.

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Communicated by G. Braus

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Ferreira, M.E.d.S., Malavazi, I., Savoldi, M. et al. Transcriptome analysis of Aspergillus fumigatus exposed to voriconazole. Curr Genet 50, 32–44 (2006). https://doi.org/10.1007/s00294-006-0073-2

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  • DOI: https://doi.org/10.1007/s00294-006-0073-2

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