title: Novel mouse model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis.
abstract: 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 (Cftr(tmlUnc-/-)) 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.
authors.affiliation: Department of Bacteriology, Institute for Medical Microbiology and Immunology, Panum Institute, University of Copenhagen, Copenhagen DK-2200, Denmark. Nadinehof@hotmail.com
authors.forename: Nadine
authors.initials: N
authors.lastname: Hoffmann
authors.forename: Thomas Bovbjerg
authors.initials: TB
authors.lastname: Rasmussen
authors.forename: Peter Østrup
authors.initials: PØ
authors.lastname: Jensen
authors.forename: Charlotte
authors.initials: C
authors.lastname: Stub
authors.forename: Morten
authors.initials: M
authors.lastname: Hentzer
authors.forename: Søren
authors.initials: S
authors.lastname: Molin
authors.forename: Oana
authors.initials: O
authors.lastname: Ciofu
authors.forename: Michael
authors.initials: M
authors.lastname: Givskov
authors.forename: Helle Krogh
authors.initials: HK
authors.lastname: Johansen
authors.forename: Niels
authors.initials: N
authors.lastname: Høiby
mesh_terms: D000464:Alginates; D000818:Animals; D002908:Chronic Disease; D003550:Cystic Fibrosis / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D020723:Glucuronic Acid / Q000096:biosynthesis; D006603:Hexuronic Acids; D006801:Humans; D008168:Lung / Q000473:pathology; D008171:Lung Diseases / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D011552:Pseudomonas Infections / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D020723:Glucuronic Acid