Role of LecA and LecB lectins in Pseudomonas aeruginosa-induced lung injury and effect of carbohydrate ligands.
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 (alpha-methyl-galactoside and alpha-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.
Chemani
Chanez
C
EA 2689, Faculté de médecine, 1 Place de Verdun, F-59045 Lille cedex, France.
Imberty
Anne
A
de Bentzmann
Sophie
S
Pierre
Maud
M
Wimmerová
Michaela
M
Guery
Benoît P
BP
Faure
Karine
K
D018829:Adhesins, Bacterial / Q000235:genetics / Q000502:physiology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001422:Bacterial Adhesion; D002241:Carbohydrates / Q000494:pharmacology; D002460:Cell Line; D004847:Epithelial Cells / Q000382:microbiology; D017353:Gene Deletion; D006801:Humans; D037102:Lectins / Q000235:genetics / Q000502:physiology*; D055370:Lung Injury; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018410:Pneumonia, Bacterial / Q000382:microbiology* / Q000473:pathology; D011552:Pseudomonas Infections / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000472:pathogenicity*; D016019:Survival Analysis; D037521:Virulence Factors / Q000235:genetics / Q000502:physiology*
D018829:Adhesins, Bacterial; D000900:Anti-Bacterial Agents; D002241:Carbohydrates; C102929:LecA protein, bacteria; C534600:LecB protein, Pseudomonas aeruginosa; D037102:Lectins; D037521:Virulence Factors