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1 January 2007

Volume 195, Number 1
The Journal of Infectious Diseases 2007;195:70–80
© 2006 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2007/19501-0009$15.00
DOI: 10.1086/509821
MAJOR ARTICLE

Stage‐Specific Adaptation of Hypermutable Pseudomonas aeruginosa Isolates during Chronic Pulmonary Infection in Patients with Cystic Fibrosis

Michael Hogardt,

Christina Hoboth,

Sabine Schmoldt,

Christine Henke,

Lutz Bader, and

Jürgen Heesemann

Max von Pettenkofer‐Institut für Hygiene und Medizinische Mikrobiologie, Ludwig‐Maximilians‐Universität, Munich, Germany

Background.Pseudomonas aeruginosa (PA) strains with defective DNA mismatch repair genes generate numerous bacterial variants because of high mutation rates. In cystic fibrosis (CF), such mutator strains may lead to the rapid selection of survivors that are specifically adapted to the hostile environment of the inflamed CF lung.

Methods.Genotypes and phenotypes of 111 PA variants descending from 3 distinct mutator strains obtained from 3 patients with CF were systematically characterized.

Results.We demonstrated that PA mutS isolates accumulated in the CF lung during the observation period of 3–6 years, with dominance during the final stage of the disease. Mutator strains from the final stage of disease were multiresistant and had lost a set of established virulence‐associated traits, including cytotoxicity for bronchial epithelial cells (Calu‐3) and macrophages (J774). This pathoadaptation was associated with the loss of survival capacity in a typical environmental habitat, such as tap water. Strikingly, nonmutator strains that maintained their virulence potential persisted as a minority, probably with a preference for the lower airways.

Conclusions.Mutator strains may evolve from the initially infecting PA strain and generate numerous variants with a loss of destructive virulence factors, probably because of selection for improved survival in the deteriorated CF lung but at the expense of the ability to live freely.

Received 6 March 2006; accepted 28 August 2006; electronically published 22 November 2006.

Reprints or correspondence: Dr. Michael Hogardt, Max von Pettenkofer‐Institut für Hygiene und Medizinische Mikrobiologie, Ludwig‐Maximilians‐Universität München, Pettenkoferstraße 9a, D‐80336 München, Germany ().

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Online publication date: 1-Jul-2009.
Abstract-Full Text-PDF Version (653 kB)
Birgitta Henriques-Normark, Christel Blomberg, Jessica Dagerhamn, Patrick Bättig, Staffan Normark. (2008) The rise and fall of bacterial clones: Streptococcus pneumoniae. Nature Reviews Microbiology 6:11, 827-837
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  • Presented in part: 10th International Congress on Pseudomonas, 27–31 August 2005, Marseille, France (talk S45).

    Potential conflicts of interest: none reported.

    Financial support: German Cystic Fibrosis Foundation (grant F06/03).

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