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Applied and Environmental Microbiology, November 2008, p. 7023-7035, Vol. 74, No. 22
0099-2240/08/$08.00+0     doi:10.1128/AEM.01288-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Bioluminescent Aspergillus fumigatus, a New Tool for Drug Efficiency Testing and In Vivo Monitoring of Invasive Aspergillosis{triangledown}

Matthias Brock,1* Grégory Jouvion,2 Sabrina Droin-Bergère,2 Olivier Dussurget,3 Marie-Anne Nicola,4 and Oumaïma Ibrahim-Granet5

Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Junior Research Group Microbial Biochemistry and Physiology, Beutenbergstr. 11a, 07745 Jena, Germany,1 Unité de Recherche et d'Expertise Histotechnologie et Pathologie, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris cedex 15, France,2 Unité des Interactions Bactéries-Cellules, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris cedex 15, France,3 Plate-Forme d'Imagerie Dynamique, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris cedex 15, France,4 Unité Cytokines & Inflammation, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris cedex 15, France5

Received 2 June 2008/ Accepted 18 September 2008

Aspergillus fumigatus is the main cause of invasive aspergillosis in immunocompromised patients, and only a limited number of drugs for treatment are available. A screening method for new antifungal compounds is urgently required, preferably an approach suitable for in vitro and in vivo studies. Bioluminescence imaging is a powerful tool to study the temporal and spatial resolutions of the infection and the effectiveness of antifungal drugs. Here, we describe the construction of a bioluminescent A. fumigatus strain by fusing the promoter of the glyceraldehyde-3-phosphate dehydrogenase gene from A. fumigatus with the luciferase gene from Photinus pyralis to control the expression of the bioluminescent reporter. A. fumigatus transformed with this construct revealed high bioluminescence under all tested growth conditions. Furthermore, light emission correlated with the number of conidia used for inoculation and with the biomass formed after different incubation times. The bioluminescent strains were suitable to study the effectiveness of antifungals in vitro by several independent methods, including the determination of light emission with a microplate reader and the direct visualization of light emission with an IVIS 100 system. Moreover, when glucocorticoid-treated immunosuppressed mice were infected with a bioluminescent strain, light emission was detected from infected lungs, allowing the visualization of the progression of invasive aspergillosis. Therefore, this new bioluminescence tool is suitable to study the in vitro effectiveness of drugs and the disease development, localization, and burden of fungi within tissues and may also provide a powerful tool to study the effectiveness of antifungals in vivo.

* Corresponding author. Mailing address: Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Junior Research Group Microbial Biochemistry and Physiology, Beutenbergstr. 11a, 07745 Jena, Germany. Phone: 49 (0)3641 5321710. Fax: 49 (0)3641 5320809. E-mail: Matthias.brock{at}hki-jena.de

{triangledown} Published ahead of print on 26 September 2008.

Applied and Environmental Microbiology, November 2008, p. 7023-7035, Vol. 74, No. 22
0099-2240/08/$08.00+0     doi:10.1128/AEM.01288-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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