The Aspergillus pH-responsive transcription factor PacC regulates virulence.
Mol Microbiol
; 55(4): 1072-84, 2005 Feb.
Article
en En
| MEDLINE
| ID: mdl-15686555
ABSTRACT
The ability of a pathogen to adapt to the host environment is usually required for the initiation of disease. Here we have investigated the importance of the Aspergillus nidulans PacC-mediated pH response in the pathogenesis of pulmonary aspergillosis. Using mutational analysis, we demonstrate that, in neutropenic mice, elimination of the A. nidulans pH-responsive transcription factor PacC, blocking the ambient pH signal transduction pathway or prevention of PacC proteolytic processing acutely attenuates virulence. Infections caused by these alkali-sensitive mutants are characterized by limited growth in vivo and a reduction of inflammatory cell infiltration. In stark contrast, constitutive activation of PacC causes increased mortality marked by extensive fungal invasive growth. PacC action is therefore required for, and able to enhance virulence, demonstrating that the A. nidulans pH-responsive transcription factor PacC plays a pivotal role in pulmonary pathogenesis.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Aspergillus nidulans
/
Factores de Transcripción
/
Proteínas Fúngicas
/
Concentración de Iones de Hidrógeno
Idioma:
En
Revista:
Mol Microbiol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
MICROBIOLOGIA
Año:
2005
Tipo del documento:
Article
País de afiliación:
Reino Unido