Molecular Characterization of the Putative Transcription Factor SebA Involved in Virulence in Aspergillus fumigatus

• DOI: 10.1128/ec.00016-12
• Publication Date: 2012-02-18T05:08:16Z
• Authors: Taísa Magnani Din...; Ricardo S. Almeida; Patrícia Alves de...; Neil Andrew Brown; Thaila Fernanda d...; Leandra Naira Zam...; Marcela Savoldi; Maria Helena S. G...; Gustavo Henrique ...
• Keywords: Invasive Pulmonary Aspergillosis; Paraquat; 0301 basic medicine; 2. Zero hunger; Mice, Inbred BALB C; Microbial Viability; Aspergillus fumigatus; Molecular Sequence Data; Hydrogen Peroxide; Oxidants; 3. Good health; Fungal Proteins; Mice; 03 medical and health sciences; Phenotype; Stress, Physiological; Gene Expression Regulation, Fungal; Animals, Outbred Strains; Animals; Calcium; Female; Amino Acid Sequence; Lung; Sequence Deletion

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 Δ sebA mutant demonstrated reduced growth in the presence of paraquat, hydrogen peroxide, CaCl 2 , 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 Δ sebA mutant. The A. fumigatus Δ sebA strain was attenuated in virulence in a murine model of invasive pulmonary aspergillosis. Furthermore, killing of the Δ sebA 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.