title: Truncated Afyap1 attenuates antifungal susceptibility of Aspergillus fumigatus to voriconazole and confers adaptation of the fungus to oxidative stress.
abstract: In yeasts truncated YAP1 homologues confer antifungal resistance. Our previous work has identified Afyap1, a YAP1 homologue, in Aspergillus fumigatus and found that it is responsible for oxidative stress in vitro. In order to decipher whether truncated Afyap1 involves in antifungal resistance mechanism and in oxidative stress adaptation in A. fumigatus, we introduce a putatively hyperactive truncated Afyap1 into wild-type A. fumigatus. We found that the resulted A. fumigatus containing truncated Afyap1 attenuated susceptibility to voriconazole and resistance to various oxidants. However, the Afyap1 deletion mutant and the strain harboring multiple copies of full-length Afyap1 had voriconazole susceptibility comparable with that of a wild-type A. fumigatus strain. Our study demonstrates that the truncated Afyap1 may involve in antifungal resistance to voriconazole in A. fumigatus and that the truncated Afyap1 sufficiently confers tolerance to oxidative stress in A. fumigatus.
authors.affiliation: Department of Dermatology, Peking University First Hospital, Peking University, West District, Beijing, People's Republic of China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Qiao
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Ruoyu
authors.initials: R
authors.lastname: Li
mesh_terms: D000222:Adaptation, Physiological; D000935:Antifungal Agents / Q000494:pharmacology*; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000235:genetics; D025141:Drug Resistance, Fungal; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D018384:Oxidative Stress; D011743:Pyrimidines / Q000494:pharmacology*; D017384:Sequence Deletion; D013312:Stress, Physiological; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014230:Triazoles / Q000494:pharmacology*; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D005656:Fungal Proteins; D011743:Pyrimidines; D014157:Transcription Factors; D014230:Triazoles; D065819:Voriconazole