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 Trichoderma atroviride seb1. The ΔsebA mutant demonstrated reduced growth in the presence of paraquat, hydrogen peroxide, CaCl₂, and poor nutritional conditions, while ΔsebA viability was also affected by heat-shock exposure. Accordingly, SebA::GFP 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 was attenuated in virulence in a murine model of invasive pulmonary aspergillosis. Furthermore, killing of the ΔsebA mutant by murine alveolar macrophages was increased when compared to the wild-type strain. A. fumigatus SebA plays a complex role, contributing to several stress tolerance pathways, growth on poor nutritional conditions and seems to be integrated in different stress responses.