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1 August 2005

Volume 192, Number 3
The Journal of Infectious Diseases 2005;192:410–419
© 2005 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2005/19203-0008$15.00
DOI: 10.1086/431516
MAJOR ARTICLE

Nonmucoid Pseudomonas aeruginosa Expresses Alginate in the Lungs of Patients with Cystic Fibrosis and in a Mouse Model

Alessandra Bragonzi,1,2

Dieter Worlitzsch,1

Gerald B. Pier,3

Petra Timpert,1

Martina Ulrich,1

Morten Hentzer,4

Jens Bo Andersen,4

Michael Givskov,4

Massimo Conese,2 and

Gerd Döring1

1Institute of Medical Microbiology and Hygiene, Universitätsklinikum Tübingen, Tübingen, Germany; 2Institute for Experimental Treatment of Cystic Fibrosis, HS Raffaele Scientific Institute, Milan, Italy; 3Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts; 4Center for Biomedical Microbiology, BioCentrum, Danish Technical University, Lyngby, Denmark

Background.In patients with cystic fibrosis (CF), lung infection with mucoid Pseudomonas aeruginosa strains overexpressing the exopolysaccaride alginate is preceded by colonization with nonmucoid strains. We investigated the kinetics, impact of environmental signals, and genetics of P. aeruginosa alginate expression in a mouse model and in patients with CF.

Methods.Using indirect immunofluorescence, microarray technology and real‐time reverse‐transcription polymerase chain reaction, we assessed alginate gene expression during aerobic and anaerobic growth of the nonmucoid strain PAO1 in vitro, in a mouse lung‐infection model and in sputum specimens from patients with CF infected with nonmucoid or mucoid P. aeruginosa strains.

Results.Anaerobic conditions increased the transcription of alginate genes in vitro and in murine lungs within 24 h. Alginate production by PAO1 in murine lungs and by nonmucoid P. aeruginosa strains in patients with CF was reversible after in vitro culture under aerobic conditions. A subpopulation of P. aeruginosa clones revealing stable alginate production was detected in murine lungs 2 weeks after infection.

Conclusions.Anaerobiosis and lung infection rapidly induce alginate production by gene regulation in nonmucoid P. aeruginosa. This trait may contribute to early persistence, leading to chronic P. aeruginosa infection once stable mucoid strains are generated.

Received 11 November 2004; accepted 23 March 2005; electronically published 24 June 2005.

Reprints or correspondence: Prof. Gerd Döring, Institute of Medical Microbiology and Hygiene, Universitätsklinikum, Wilhelmstr. 31, D‐72074 Tübingen, Germany ().

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  • Presented in part: 26th Congress of the European Cystic Fibrosis Society, Belfast, Northern Ireland, 4–7 June 2003; 17th Annual North American Cystic Fibrosis Conference, Anaheim, California, 16–19 October 2003.

    Financial support: Marie Curie Fellowship (grant MCFI‐2001‐51061); Mukoviszidose; Cystic Fibrosis Foundation; National Institutes of Health (grant AI48917); Associazione Lombarda Fibrosi Cistica.

    Potential conflicts of interest: none reported.

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