TY - JOUR

T1 - Novel mouse model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis

AU - Hoffmann, Nadine

AU - Rasmussen, Thomas Bovbjerg

AU - Jensen, Peter Østrup

AU - Stub, Charlotte

AU - Hentzer, Morten

AU - Molin, Søren

AU - Ciofu, Oana

AU - Givskov, Michael

AU - Johansen, Helle Krogh

AU - Høiby, Niels

N1 - Keywords: Alginates; Animals; Chronic Disease; Cystic Fibrosis; Disease Models, Animal; Female; Glucuronic Acid; Hexuronic Acids; Humans; Lung; Lung Diseases; Male; Mice; Mice, Inbred BALB C; Phenotype; Pseudomonas Infections; Signal Transduction

PY - 2005

Y1 - 2005

N2 - 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.

AB - 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.

U2 - 10.1128/IAI.73.4.2504-2514.2005

DO - 10.1128/IAI.73.4.2504-2514.2005

M3 - Journal article

C2 - 15784597

VL - 73

SP - 2504

EP - 2514

JO - Infection and Immunity

JF - Infection and Immunity

SN - 0019-9567

IS - 4

ER -