Novel experimental Pseudomonas aeruginosa lung infection model mimicking long-term host-pathogen interactions in cystic fibrosis.
The dominant cause of premature death in patients suffering from cystic fibrosis (CF) is chronic lung infection with Pseudomonas aeruginosa. The chronic lung infection often lasts for decades with just one clone. However, as a result of inflammation, antibiotic treatment and different niches in the lungs, the clone undergoes significant genetic changes, resulting in diversifying geno- and phenotypes. Such an adaptation may generate different host responses. To experimentally reflect the year-long chronic lung infection in CF, groups of BALB/c mice were infected with clonal isolates from different periods (1980, 1988, 1997, 1999 and 2003) of the chronic lung infection of one CF patient using the seaweed alginate embedment model. The results showed that the non-mucoid clones reduced their virulence over time, resulting in faster clearing of the bacteria from the lungs, improved pathology and reduced pulmonary production of macrophage inflammatory protein-2 (MIP-2) and granulocyte colony-stimulating factor (G-CSF). In contrast, the mucoid clones were more virulent and virulence increased with time, resulting in impaired pulmonary clearing of the latest clone, severe inflammation and increased pulmonary MIP-2 and G-CSF production. In conclusion, adaptation of P. aeruginosa in CF is reflected by changed ability to establish lung infection and results in distinct host responses to mucoid and non-mucoid phenotypes.
Moser
Claus
C
Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Van Gennip
Maria
M
Bjarnsholt
Thomas
T
Jensen
Peter Østrup
PØ
Lee
Baoleri
B
Hougen
Hans Petter
HP
Calum
Henrik
H
Ciofu
Oana
O
Givskov
Michael
M
Molin
Søren
S
Høiby
Niels
N
D000818:Animals; D054426:Chemokine CXCL2 / Q000096:biosynthesis; D003550:Cystic Fibrosis / Q000382:microbiology*; D004195:Disease Models, Animal; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis; D006801:Humans; D008168:Lung / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011552:Pseudomonas Infections / Q000209:etiology* / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification* / Q000472:pathogenicity; D014774:Virulence
D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D016179:Granulocyte Colony-Stimulating Factor