Afyap1, encoding a bZip transcriptional factor ofAspergillus fumigatus, contributes to oxidative stress response but is not essential to the virulence of this pathogen in mice immunosuppressed by cyclophosphamide and triamcinolone
Autor: | Zhe Wan, Dimitrios P. Kontoyiannis, Ruoyu Li, Dongmei Li, Jianjun Qiao, Yan Ma, Wei Liu, Richard Calderone |
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Rok vydání: | 2008 |
Předmět: |
Molecular Sequence Data
Virulence Biology Triamcinolone medicine.disease_cause Marker gene Aspergillus fumigatus Microbiology Fungal Proteins Mice chemistry.chemical_compound Menadione Gene Expression Regulation Fungal medicine Animals Amino Acid Sequence skin and connective tissue diseases Cyclophosphamide Pathogen Invasive Pulmonary Aspergillosis YAP1 chemistry.chemical_classification Mice Inbred BALB C Phagocytes Reactive oxygen species General Medicine biology.organism_classification Disease Models Animal Oxidative Stress Basic-Leucine Zipper Transcription Factors Infectious Diseases chemistry Reactive Oxygen Species Gene Deletion Immunosuppressive Agents Oxidative stress |
Zdroj: | Medical Mycology. 46:773-782 |
ISSN: | 1460-2709 1369-3786 |
Popis: | Aspergillus fumigatus, an important human fungal pathogen, encounters high levels of reactive oxygen species following its ingestion by phagocytes. Reactive oxygen species are important mediators of the fungicidal activities of phagocytes. In yeasts, YAP1 encodes for transcriptional factors that contribute to their oxidative stress response and given the importance of the stress response, we hypothesized that the YAP1 homologue in A. fumigatus plays a similar role in this fungus. In this study, we found that Afyap1, the Yap1 homologue of A. fumigatus, confers protection against oxidative stress. Replacement of Afyap1 with the marker gene pyrG (DeltaAfyap1) resulted in hypersensitivity of A. fumigatus to oxidants such as H(2)O(2) and menadione. In contrast, an A. fumigatus strain harboring multiple-copy Afyap1 was resistant to these two oxidants as well as the oxidant diamide. However, DeltaAfyap1 and strain harboring multiple-copy Afyap1 were comparable in their virulence to a wild-type A. fumigatus strain in a murine model of invasive pulmonary aspergillosis. Taken together, these results demonstrate that Afyap1 is involved in oxidative stress response but is not an essential virulence factor for A. fumigatus. |
Databáze: | OpenAIRE |
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