title: NosA, a transcription factor important in Aspergillus fumigatus stress and developmental response, rescues the germination defect of a laeA deletion.
abstract: Aspergillus fumigatus is an increasingly serious pathogen of immunocompromised patients, causing the often fatal disease invasive aspergillosis (IA). One A. fumigatus virulence determinant of IA is LaeA, a conserved virulence factor in pathogenic fungi. To further understand the role of LaeA in IA, the expression profile of ΔlaeA was compared to wild type, and several transcription factors were found significantly misregulated by LaeA loss. One of the transcription factors up-regulated over 4-fold in the ΔlaeA strain was Afu4g09710, similar in sequence to Aspergillus nidulans NosA, which is involved in sexual development. Here we assessed loss of nosA (ΔnosA) and overexpression of nosA (OE::nosA) on A. fumigatus in both a wild type and ΔlaeA background. Based on the multiple alterations of physiological development of single and double mutants, we suggest that NosA mediates the decreased radial growth and delayed conidial germination observed in ΔlaeA strains, the former in a light dependent manner. The ΔnosA mutant showed increased virulence in the Galleria mellonella larvae model of disseminated aspergillosis, potentially due to its increased growth and germination rate. Furthermore, the A. fumigatus nosA allele was able to partially remediate sexual development in an A. nidulans ΔnosA background. Likewise, the A. nidulans nosA allele was able to restore the menadione sensitivity defect of the A. fumigatus ΔnosA strain, suggesting conservation of function of the NosA protein in these two species.
authors.affiliation: Department of Genetics, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Alexandra A
authors.initials: AA
authors.lastname: Soukup
authors.forename: Mitra
authors.initials: M
authors.lastname: Farnoodian
authors.forename: Erwin
authors.initials: E
authors.lastname: Berthier
authors.forename: Nancy P
authors.initials: NP
authors.lastname: Keller
mesh_terms: D000818:Animals; D001228:Aspergillosis / Q000382:microbiology*; D001232:Aspergillus fumigatus / Q000235:genetics / Q000254:growth & development / Q000378:metabolism* / Q000472:pathogenicity; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D009036:Moths; D013172:Spores, Fungal / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
chemical_list: D005656:Fungal Proteins; D014157:Transcription Factors