TY - JOUR
T1 - Molecular characterization of the putative transcription factor SebA involved in virulence in Aspergillus fumigatus
AU - Dinamarco, Taísa Magnani
AU - Almeida, Ricardo S.
AU - de Castro, Patrícia Alves
AU - Brown, Neil Andrew
AU - dos Reis, Thaila Fernanda
AU - Ramalho, Leandra Naira Zambelli
AU - Savoldi, Marcela
AU - Goldman, Maria Helena S
AU - Goldman, Gustavo Henrique
PY - 2012/4/1
Y1 - 2012/4/1
N2 - 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, 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 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.
AB - 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, 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 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.
UR - http://www.scopus.com/inward/record.url?scp=84859148914&partnerID=8YFLogxK
U2 - 10.1128/EC.00016-12
DO - 10.1128/EC.00016-12
M3 - Article
C2 - 22345349
AN - SCOPUS:84859148914
SN - 1535-9778
VL - 11
SP - 518
EP - 531
JO - Eukaryotic Cell
JF - Eukaryotic Cell
IS - 4
ER -