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Infection and Immunity, May 2009, p. 2065-2075, Vol. 77, No. 5
0019-9567/09/$08.00+0 doi:10.1128/IAI.01204-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

* and
Karine Faure1,
EA 2689, IFR 114, Faculté de Médecine, Université de Lille 2 and CHRU de Lille, Lille, France,1 CERMAV-CNRS, Grenoble, France,2 UPR9027 CNRS, IFR88, Systèmes membranaires et pathogénicité chez Pseudomonas aeruginosa, Marseille, France,3 EA 3925, IFR 114, Clinique de Pédiatrie, Hôpital Jeanne de Flandre, Université de Lille 2 and CHRU de Lille, Lille, France,4 NCBR and Department of Biochemistry, Masaryk University, Brno, Czech Republic5
Received 29 September 2008/ Returned for modification 14 November 2008/ Accepted 17 February 2009
Pseudomonas aeruginosa is a frequently encountered pathogen that is involved in acute and chronic lung infections. Lectin-mediated bacterium-cell recognition and adhesion are critical steps in initiating P. aeruginosa pathogenesis. This study was designed to evaluate the contributions of LecA and LecB to the pathogenesis of P. aeruginosa-mediated acute lung injury. Using an in vitro model with A549 cells and an experimental in vivo murine model of acute lung injury, we compared the parental strain to lecA and lecB mutants. The effects of both LecA- and Lec B-specific lectin-inhibiting carbohydrates (
-methyl-galactoside and
-methyl-fucoside, respectively) were evaluated. In vitro, the parental strain was associated with increased cytotoxicity and adhesion on A549 cells compared to the lecA and lecB mutants. In vivo, the P. aeruginosa-induced increase in alveolar barrier permeability was reduced with both mutants. The bacterial burden and dissemination were decreased for both mutants compared with the parental strain. Coadministration of specific lectin inhibitors markedly reduced lung injury and mortality. Our results demonstrate that there is a relationship between lectins and the pathogenicity of P. aeruginosa. Inhibition of the lectins by specific carbohydrates may provide new therapeutic perspectives.
Published ahead of print on 23 February 2009.
B.P.G. and K.F. contributed equally to this work.
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