title: Afyap1, encoding a bZip transcriptional factor of Aspergillus fumigatus, contributes to oxidative stress response but is not essential to the virulence of this pathogen in mice immunosuppressed by cyclophosphamide and triamcinolone.
abstract: 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.
authors.affiliation: Department of Dermatology, Peking University First Hospital, and Research Center for Medical Mycology, Peking University, Beijing, the People's Republic of China. lrymm@medmail.com.cn
authors.forename: Jianjun
authors.initials: J
authors.lastname: Qiao
authors.forename: Dimitrios P
authors.initials: DP
authors.lastname: Kontoyiannis
authors.forename: Richard
authors.initials: R
authors.lastname: Calderone
authors.forename: Dongmei
authors.initials: D
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wan
authors.forename: Ruoyu
authors.initials: R
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001232:Aspergillus fumigatus / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000472:pathogenicity*; D050976:Basic-Leucine Zipper Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D003520:Cyclophosphamide / Q000494:pharmacology; D004195:Disease Models, Animal; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D007166:Immunosuppressive Agents / Q000494:pharmacology; D055744:Invasive Pulmonary Aspergillosis / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D018384:Oxidative Stress; D010586:Phagocytes / Q000187:drug effects / Q000276:immunology; D017382:Reactive Oxygen Species / Q000378:metabolism; D014221:Triamcinolone / Q000494:pharmacology; D014774:Virulence
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D005656:Fungal Proteins; D007166:Immunosuppressive Agents; D017382:Reactive Oxygen Species; D014221:Triamcinolone; D003520:Cyclophosphamide