Novel experimental Pseudomonas aeruginosa lung infection model mimicking long-term host-pathogen interactions in cystic fibrosis

Claus Moser, Maria van Gennip, Thomas Bjarnsholt, Peter Ostrup Jensen, Baoleri Lee, Hans Petter Hougen, Henrik Calum, Oana Ciofu, Michael Christian Givskov, Søren Molin, Niels Hoiby

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    Abstract

    Moser C, van Gennip M, Bjarnsholt T, Jensen PO, Lee B, Hougen HP, Calum H, Ciofu O, Givskov M, Molin S, Hoiby N. Novel experimental Pseudomonas aeruginosa lung infection model mimicking long-term host-pathogen interactions in cystic fibrosis. APMIS 2009; 117: 95-107. 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.
    Original languageEnglish
    JournalActa Pathologica Microbiologica et Immunologica Scandinavica
    Volume117
    Issue number2
    Pages (from-to)95-107
    ISSN0903-4641
    DOIs
    Publication statusPublished - 2009

    Keywords

    • cystic fibrosis
    • host response
    • Pseudomonas aeruginosa
    • chronic lung infection
    • adaptation

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