Binding of the galactose-specificPseudomonas aeruginosa lectin, PA-I, to glycosphingolipids and other glycoconjugates

Lanne, Boel; Ciopraga, J.; Bergström, Jakob; Motas, Cecilia; Karlsson, Karl‐Anders

doi:10.1007/bf00731201

Cited by 44 publications

(30 citation statements)

References 37 publications

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“…for P. aeruginosa (15). LecA is a D-galactose-binding lectin with high affinity for terminal glycans presenting an ␣-galactose residue at the nonreducing end (4,18). The LecB lectin has a high affinity for L-fucose and its derivatives (24,35).…”

Section: Discussionmentioning

confidence: 99%

Role of LecA and LecB Lectins in Pseudomonas aeruginosa -Induced Lung Injury and Effect of Carbohydrate Ligands

et al. 2009

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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.

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Section: Discussionmentioning

confidence: 99%

Role of LecA and LecB Lectins in Pseudomonas aeruginosa -Induced Lung Injury and Effect of Carbohydrate Ligands

et al. 2009

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“…Strong binding was observed to the galabiose compounds, which were previously noted to be strong monovalent ligands. [37] Strikingly in the galactose case, strong binding was only detected to the di-and tetravalent conjugates but not to the monovalent. This is in agreement with the interbinding site distance of this lectin.…”

Section: Binding Experiments With a Series Of Lectinsmentioning

confidence: 93%

Rapid Screening of Lectins for Multivalency Effects with a Glycodendrimer Microarray

et al. 2010

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Multivalency is an important phenomenon in protein-carbohydrate interactions. In order to evaluate glycodendrimers as multivalent inhibitors of carbohydrate binding proteins, we displayed them on a microarray surface. Valencies were varied from 1 to 8, and corrections were made for the valencies so that all surfaces contained the same amount of the sugar ligand. Five different carbohydrates were attached to the dendrimers. A series of fluorescent lectins was evaluated, and for each of them a binding profile was obtained from a single experiment showing both the specificity of the lectin for a certain sugar and whether it prefers multivalent ligands or not. Very distinct binding patterns were seen for the various lectins. The results were rationalized with respect to the interbinding distances of the lectins.

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“…Recent observations suggest that GSLs might be of critical importance for the internalization of P. aeruginosa into nonphagocytic cells (9). The homotetrameric, galactophilic lectin LecA, which is localized to the outer bacterial membrane (21), belongs to the carbohydrate binding proteins expressed by P. aeruginosa that recognize GSLs (22,23) and represents one of the virulence factors (24). The preferential binding of LecA to the GSL globotriaosylceramide (also known as Gb3/CD77 or Pk histo-blood group antigen) (22,25) prompted us to investigate the role of LecA-Gb3 interaction in the cellular uptake of P. aeruginosa.…”

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confidence: 99%

A lipid zipper triggers bacterial invasion

Eierhoff

Bastian

Thuenauer

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

128

161

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Significance Entry of bacteria into host cells critically depends on their proper engulfment by the plasma membrane. So far, actin polymerization has been described as a major driving force in this process. However, our study reveals that the interaction of the bacterial surface lectin LecA with the host cell glycosphingolipid Gb3 is fully sufficient to promote engulfment of Pseudomonas aeruginosa , whereas actin polymerization is dispensable. Hence, the formation of a “lipid zipper” represents a previously unidentified mechanism of bacterial uptake and demonstrates that bacterial pathogens have evolved lipid-based invasion strategies that may function in addition to protein receptor-based ones. Furthermore, by identifying the LecA/Gb3 interaction as the major invasion-promoting factor, our study provides new targets for drugs that may prevent bacterial invasion and dissemination.

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Binding of the galactose-specificPseudomonas aeruginosa lectin, PA-I, to glycosphingolipids and other glycoconjugates

Cited by 44 publications

References 37 publications

Role of LecA and LecB Lectins in Pseudomonas aeruginosa -Induced Lung Injury and Effect of Carbohydrate Ligands

Role of LecA and LecB Lectins in Pseudomonas aeruginosa -Induced Lung Injury and Effect of Carbohydrate Ligands

Rapid Screening of Lectins for Multivalency Effects with a Glycodendrimer Microarray

A lipid zipper triggers bacterial invasion

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