Pseudomonas aeruginosa microevolution during cystic fibrosis lung infection establishes clones with adapted virulence

Alessandra Bragonzi, Moira Paroni, Alessandro Nonis, Nina Cramer, Sara Montanari, Joanna Rejman, Clelia Di Serio, Gerd Döring, Burkhard Tümmler

Research output: Contribution to journalArticle

Abstract

Rationale: During long-term lung infection in patients with cystic fibrosis (CF), Pseudomonas aeruginosa strains develop mutations leading to clonal expansion. This microevolution is believed to be correlated with a reduced virulence. Objectives: We tested this hypothesis in models of lung infection, using mice with different genetic backgrounds. Methods: From infected airways of six patients with CF, 25 P. aeruginosa clones were isolated during a period of up to 16.3 years and genotypically and phenotypically characterized. Virulence of the 8 early, 6 intermediate, and 11 late CF isolates and 5 environmental strains was assessed by monitoring acute mortality versus survival and P. aeruginosa chronic persistence versus lung clearance in mice of different genetic backgrounds, including CF mice. Measurements and Main Results: Different patients harbored clonally unrelated strains, but early, intermediate, and late P. aeruginosa isolates from single patients were clonally related, allowing comparative in vivo analysis. Although late isolates were attenuated in causing acute mortality in the mouse models, compared with early and intermediate clonal isolates and environmental strains, they did not differfromearlyandintermediate clonal isolates in their capacity to establish chronic infection and cause extensive inflammation in the murine respiratory tract. Conclusions: Our findings indicate that clonal expansion of P. aeruginosa strains during microevolution within CF lungs leads to populations with altered but not reduced virulence. These P. aeruginosa clones with adapted virulence play a critical role in the pathogenesis of chronic infections andmay serve to define virulence determinants as targets for novel therapies.

Original languageEnglish
Pages (from-to)138-145
Number of pages8
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume180
Issue number2
DOIs
Publication statusPublished - Jul 15 2009

Keywords

  • Biological adaptation
  • Cystic fibrosis
  • Pseudomonas infection
  • Respiratory tract infections

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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