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
SN - 0019-9567
VL - 73
SP - 2504
EP - 2514
JO - Infection and Immunity
JF - Infection and Immunity
IS - 4
ER -