title: Molecular characterization of the putative transcription factor SebA involved in virulence in Aspergillus fumigatus.
abstract: Aspergillus fumigatus is a major opportunistic pathogen and allergen of mammals. Nutrient sensing and acquisition mechanisms, as well as the capability to cope with different stressing conditions, are essential for A. fumigatus virulence and survival in the mammalian host. This study characterized the A. fumigatus SebA transcription factor, which is the putative homologue of the factor encoded by Trichoderma atroviride seb1. The ΔsebA mutant demonstrated reduced growth in the presence of paraquat, hydrogen peroxide, CaCl2, and poor nutritional conditions, while viability associated with sebA was also affected by heat shock exposure. Accordingly, SebA::GFP (SebA::green fluorescent protein) was shown to accumulate in the nucleus upon exposure to oxidative stress and heat shock conditions. In addition, genes involved in either the oxidative stress or heat shock response had reduced transcription in the ΔsebA mutant. The A. fumigatus ΔsebA strain was attenuated in virulence in a murine model of invasive pulmonary aspergillosis. Furthermore, killing of the ΔsebA mutant by murine alveolar macrophages was increased compared to killing of the wild-type strain. A. fumigatus SebA plays a complex role, contributing to several stress tolerance pathways and growth under poor nutritional conditions, and seems to be integrated into different stress responses.
authors.affiliation: Laboratório Nacional de Ciência e Tecnologia do Bioetanol-CTBE, São Paulo, Brazil.
authors.forename: Taísa Magnani
authors.initials: TM
authors.lastname: Dinamarco
authors.forename: Ricardo S
authors.initials: RS
authors.lastname: Almeida
authors.forename: Patrícia Alves
authors.initials: PA
authors.lastname: de Castro
authors.forename: Neil Andrew
authors.initials: NA
authors.lastname: Brown
authors.forename: Thaila Fernanda
authors.initials: TF
authors.lastname: dos Reis
authors.forename: Leandra Naira Zambelli
authors.initials: LN
authors.lastname: Ramalho
authors.forename: Marcela
authors.initials: M
authors.lastname: Savoldi
authors.forename: Maria Helena S
authors.initials: MH
authors.lastname: Goldman
authors.forename: Gustavo Henrique
authors.initials: GH
authors.lastname: Goldman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D021461:Animals, Outbred Strains; D001232:Aspergillus fumigatus / Q000254:growth & development / Q000472:pathogenicity / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D005260:Female; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D006861:Hydrogen Peroxide / Q000494:pharmacology; D055744:Invasive Pulmonary Aspergillosis / Q000276:immunology / Q000382:microbiology; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D050296:Microbial Viability / Q000187:drug effects; D008969:Molecular Sequence Data; D016877:Oxidants / Q000494:pharmacology; D010269:Paraquat / Q000494:pharmacology; D010641:Phenotype; D017384:Sequence Deletion; D013312:Stress, Physiological / Q000187:drug effects; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014774:Virulence; D016335:Zinc Fingers
chemical_list: D005656:Fungal Proteins; D016877:Oxidants; D014157:Transcription Factors; D006861:Hydrogen Peroxide; D010269:Paraquat; D002118:Calcium