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Infection and Immunity, April 2005, p. 2504-2514, Vol. 73, No. 4
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.4.2504-2514.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Novel Mouse Model of Chronic Pseudomonas aeruginosa Lung Infection Mimicking Cystic Fibrosis

Nadine Hoffmann,1* Thomas Bovbjerg Rasmussen,2 PeterØstrup Jensen,1 Charlotte Stub,3 Morten Hentzer,2 Søren Molin,2 Oana Ciofu,1 Michael Givskov,2 Helle Krogh Johansen,1 and Niels Høiby1

Department of Clinical Microbiology, Rigshospitalet, and Department of Bacteriology, Institute for Medical Microbiology and Immunology, Panum Institute, University of Copenhagen, Copenhagen,1 BioCentrum-DTU, Technical University of Denmark, Lyngby,2 Department of Pharmacology and Pathobiology, Royal Veterinary and Agricultural University, Frederiksberg, Denmark3

Received 25 June 2004/ Returned for modification 5 August 2004/ Accepted 5 October 2004

Pseudomonas aeruginosa causes a chronic infection in the lungs of cystic fibrosis (CF) patients by establishing an alginate-containing biofilm. The infection has been studied in several animal models; however, most of the models required artificial embedding of the bacteria. We present here a new pulmonary mouse model without artificial embedding. The model is based on a stable mucoid CF sputum isolate (NH57388A) with hyperproduction of alginate due to a deletion in mucA and functional N-acylhomoserine lactone (AHL)-based quorum-sensing systems. Chronic lung infection could be established in both CF mice (CftrtmlUnc–/–) and BALB/c mice, as reflected by the detection of a high number of P. aeruginosa organisms in the lung homogenates at 7 days postinfection and alginate biofilms, surrounded by polymorphonuclear leukocytes in the alveoli. In comparison, both an AHL-producing nonmucoid revertant (NH57388C) from the mucoid isolate (NH57388A) and a nonmucoid isolate (NH57388B) deficient in AHL were almost cleared from the lungs of the mice. This model, in which P. aeruginosa is protected against the defense system of the lung by alginate, is similar to the clinical situation. Therefore, the mouse model provides an improved method for evaluating the interaction between mucoid P. aeruginosa, the host, and antibacterial therapy.

* Corresponding author. Mailing address: Department of Bacteriology, Institute for Medical Microbiology and Immunology, Panum Institute, University of Copenhagen, Copenhagen DK-2200, Denmark. Phone: (45) 35327890. Fax: (45) 35327693. E-mail: Nadinehof{at}hotmail.com.

Editor: J. T. Barbieri

Infection and Immunity, April 2005, p. 2504-2514, Vol. 73, No. 4
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.4.2504-2514.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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