This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Smith, J M Articles by Holden, D W Search for Related Content PubMed PubMed Citation Articles by Smith, J M Articles by Holden, D W

research-article

Virulence of Aspergillus fumigatus double mutants lacking restriction and an alkaline protease in a low-dose model of invasive pulmonary aspergillosis.

Department of Infectious Diseases and Bacteriology, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.

ABSTRACT

To investigate the pathogenicity of Aspergillus fumigatus mutants lacking putative virulence factors, we have developed a new murine model of invasive pulmonary aspergillosis based on neutropenia, the major factor predisposing patients to this infection. Mice were treated with cyclophosphamide and inoculated by the intranasal route with 5 x 10(3) conidia, a significant reduction from inoculum levels used in previous models. Evidence for the production of the extracellular alkaline protease (Alp) in lung tissue was obtained by using a fungal transformant harboring an alp::lacZ reporter gene fusion. The pathogenicities of single mutant strains lacking either Alp or the ribotoxin restrictocin and of a double mutant strain lacking both proteins were assessed in this infection model. There were no significant differences between the mutant and the wild-type strains in terms of mortality or histological-features. Inoculations with mixtures of conidia showed that the double mutant strain is slightly less virulent than the wild-type strain. We conclude that Alp and restrictocin are not important virulence determinants in pulmonary infection.

This article has been cited by other articles:

• Mellado, E., Garcia-Effron, G., Buitrago, M. J., Alcazar-Fuoli, L., Cuenca-Estrella, M., Rodriguez-Tudela, J. L. (2005). Targeted Gene Disruption of the 14-{alpha} Sterol Demethylase (cyp51A) in Aspergillus fumigatus and Its Role in Azole Drug Susceptibility. Antimicrob. Agents Chemother. 49: 2536-2538 [Abstract] [Full Text]  
• Stephens-Romero, S. D., Mednick, A. J., Feldmesser, M. (2005). The Pathogenesis of Fatal Outcome in Murine Pulmonary Aspergillosis Depends on the Neutrophil Depletion Strategy. Infect. Immun. 73: 114-125 [Abstract] [Full Text]  
• Liebmann, B., Muller, M., Braun, A., Brakhage, A. A. (2004). The Cyclic AMP-Dependent Protein Kinase A Network Regulates Development and Virulence in Aspergillus fumigatus. Infect. Immun. 72: 5193-5203 [Abstract] [Full Text]  
• Bhabhra, R., Miley, M. D., Mylonakis, E., Boettner, D., Fortwendel, J., Panepinto, J. C., Postow, M., Rhodes, J. C., Askew, D. S. (2004). Disruption of the Aspergillus fumigatus Gene Encoding Nucleolar Protein CgrA Impairs Thermotolerant Growth and Reduces Virulence. Infect. Immun. 72: 4731-4740 [Abstract] [Full Text]  
• Naglik, J. R., Challacombe, S. J., Hube, B. (2003). Candida albicans Secreted Aspartyl Proteinases in Virulence and Pathogenesis. Microbiol. Mol. Biol. Rev. 67: 400-428 [Abstract] [Full Text]  
• Magee, P. T., Gale, C., Berman, J., Davis, D. (2003). Molecular Genetic and Genomic Approaches to the Study of Medically Important Fungi. Infect. Immun. 71: 2299-2309 [Full Text]  
• Panepinto, J. C., Oliver, B. G., Fortwendel, J. R., Smith, D. L. H., Askew, D. S., Rhodes, J. C. (2003). Deletion of the Aspergillus fumigatus Gene Encoding the Ras-Related Protein RhbA Reduces Virulence in a Model of Invasive Pulmonary Aspergillosis. Infect. Immun. 71: 2819-2826 [Abstract] [Full Text]  
• Wang, Z., Zheng, L., Liu, H., Wang, Q., Hauser, M., Kauffman, S., Becker, J. M., Szaniszlo, P. J. (2001). WdChs2p, a Class I Chitin Synthase, Together with WdChs3p (Class III) Contributes to Virulence in Wangiella (Exophiala) dermatitidis. Infect. Immun. 69: 7517-7526 [Abstract] [Full Text]  
• Weig, M., Frosch, M., Tintelnot, K., Haas, A., Groß, U., Linsmeier, B., Heesemann, J. (2001). Use of Recombinant Mitogillin for Improved Serodiagnosis of Aspergillus fumigatus-Associated Diseases. J. Clin. Microbiol. 39: 1721-1730 [Abstract] [Full Text]  
• Latge, J.-P. (1999). Aspergillus fumigatus and Aspergillosis. Clin. Microbiol. Rev. 12: 310-350 [Abstract] [Full Text]  
• Woods, J. P., Retallack, D. M., Heinecke, E. L., Goldman, W. E. (1998). Rare Homologous Gene Targeting in Histoplasma capsulatum: Disruption of the URA5Hc Gene by Allelic Replacement. J. Bacteriol. 180: 5135-5143 [Abstract] [Full Text]  
• Tsai, H.-F., Chang, Y. C., Washburn, R. G., Wheeler, M. H., Kwon-Chung, K. J. (1998). . J. Bacteriol. 180: 3031-3038 [Abstract] [Full Text]  
• Woods, J. P., Heinecke, E. L., Goldman, W. E. (1998). Electrotransformation and Expression of Bacterial Genes Encoding Hygromycin Phosphotransferase and beta -Galactosidase in the Pathogenic Fungus Histoplasma capsulatum. Infect. Immun. 66: 1697-1707 [Abstract] [Full Text]