Role of laeA in the regulation of alb1, gliP, conidial morphology and virulence in Aspergillus fumigatus
Author:
Sugui JA, Pardo J, Chang YC, Müllbacher A, Zarember KA, Galvez EM, Brinster L, Zerfas P, Gallin JI, Simon MM, Kwon-Chung KJ
Date: 2 August 2007
Abstract:
The alb1 (pksP) gene was reported as a virulence factor controlling pigment and morphology of conidia in Aspergillus fumigatus. A recent report suggested that laeA regulates alb1 expression and conidial morphology but not pigment in the A. fumigatus strain AF293. laeA was also reported to regulate synthesis of secondary metabolites, such as gliotoxin. We compared the role of laeA in the regulation of conidial morphology and expression of alb1 and gliP in the strains B-5233 and AF293, which differ in colony morphology and nutritional requirements. Deletion of laeA did not affect conidial morphology or pigmentation in these strains, suggesting that laeA is not involved in alb1 regulation during conidial morphogenesis. Deletion of laeA, however, caused down-regulation of alb1 during mycelial growth in liquid media. Transcription of gliP, involved in the synthesis of gliotoxin, was drastically reduced in B-5233laeADelta and the gliotoxin found in the culture filtrates was 20% of wild type concentrations. While up-regulation of gliP in AF293 was comparably high to B-5233, the relative mRNA level in AF293laeADelta was about 4-fold lower compared to B-5233laeADelta. The B-5233laeADelta strain caused slower onset of fatal infection in mice compared to B-5233. Histopathology from lungs of infected mice corroborated the survival data. Culture filtrates from B-5233laeADelta caused reduced death in thymoma cells and were less inhibitory to respiratory burst of neutrophils compared to that of B-5233. Our results suggest that while laeA is not involved in the regulation of alb1 function in conidial morphology, it regulates the synthesis of gliotoxin and virulence of A. fumigatus.
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