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Eukaryotic Cell, September 2007, p. 1552-1561, Vol. 6, No. 9
1535-9778/07/$08.00+0     doi:10.1128/EC.00140-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Role of laeA in the Regulation of alb1, gliP, Conidial Morphology, and Virulence in Aspergillus fumigatus{triangledown}

Janyce A. Sugui,1 Julian Pardo,2 Yun C. Chang,1 Arno Müllbacher,6 Kol A. Zarember,3 Eva M. Galvez,5 Lauren Brinster,4 Patricia Zerfas,4 John I. Gallin,3 Markus M. Simon,2 and Kyung J. Kwon-Chung1*

Laboratory of Clinical Infectious Diseases,1 Laboratory of Host Defense,3 Office of Research Services, National Institutes of Health, Bethesda, Maryland,4 Max Planck Institute of Immunology,2 Institut für Physikalische Chemie, Freiburg Universität, Freiburg, Germany,5 John Curtin School of Medical Research, Australian National University, Canberra, Australia6

Received 24 April 2007/ Accepted 29 June 2007

The alb1 (pksP) gene has been reported as a virulence factor controlling the pigmentation and morphology of conidia in Aspergillus fumigatus. A recent report suggested that laeA regulates alb1 expression and conidial morphology but not pigmentation in the A. fumigatus strain AF293. laeA has also been reported to regulate the synthesis of secondary metabolites, such as gliotoxin. We compared the role of laeA in the regulation of conidial morphology and the expression of alb1 and gliP in 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 a liquid medium. Transcription of gliP, involved in the synthesis of gliotoxin, was drastically reduced in B-5233laeA{Delta}, and the gliotoxin level found in the culture filtrates was 20% of wild-type concentrations. While up-regulation of gliP in AF293 was comparable to that in B-5233, the relative mRNA level in AF293laeA{Delta} was about fourfold lower than that in B-5233laeA{Delta}. Strain B-5233laeA{Delta} caused slower onset of fatal infection in mice relative to that with B-5233. Histopathology of sections from lungs of infected mice corroborated the survival data. Culture filtrates from B-5233laeA{Delta} caused reduced death in thymoma cells and were less inhibitory to a respiratory burst of neutrophils than culture filtrates from 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 the virulence of A. fumigatus.

* Corresponding author. Mailing address: Molecular Microbiology Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892. Phone: (301) 496-1602. Fax: (301) 480-3240. E-mail: june_kwon-chung{at}nih.gov

{triangledown} Published ahead of print on 13 July 2007.

Eukaryotic Cell, September 2007, p. 1552-1561, Vol. 6, No. 9
1535-9778/07/$08.00+0     doi:10.1128/EC.00140-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Ma, Y., Qiao, J., Liu, W., Wan, Z., Wang, X., Calderone, R., Li, R. (2008). The Sho1 Sensor Regulates Growth, Morphology, and Oxidant Adaptation in Aspergillus fumigatus but Is Not Essential for Development of Invasive Pulmonary Aspergillosis. Infect. Immun. 76: 1695-1701 [Abstract] [Full Text]  
  • Sugui, J. A., Pardo, J., Chang, Y. C., Zarember, K. A., Nardone, G., Galvez, E. M., Mullbacher, A., Gallin, J. I., Simon, M. M., Kwon-Chung, K. J. (2007). Gliotoxin Is a Virulence Factor of Aspergillus fumigatus: gliP Deletion Attenuates Virulence in Mice Immunosuppressed with Hydrocortisone. Eukaryot Cell 6: 1562-1569 [Abstract] [Full Text]  


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