Inhibition of the bacterial lectins of Pseudomonas aeruginosa with monosaccharides and peptides.
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Inhibition of the bacterial lectins of Pseudomonas aeruginosa with monosaccharides and peptides. / Gustke, Heike; Kleene, Ralf; Loers, Gabriele; Nehmann, Nina; Jaehne, M; Bartels, K-M; Jaeger, K-E; Schachner, Melitta; Schumacher, Udo.
In: EUR J CLIN MICROBIOL, Vol. 31, No. 2, 2, 2012, p. 207-215.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Inhibition of the bacterial lectins of Pseudomonas aeruginosa with monosaccharides and peptides.
AU - Gustke, Heike
AU - Kleene, Ralf
AU - Loers, Gabriele
AU - Nehmann, Nina
AU - Jaehne, M
AU - Bartels, K-M
AU - Jaeger, K-E
AU - Schachner, Melitta
AU - Schumacher, Udo
PY - 2012
Y1 - 2012
N2 - Pseudomonas aeruginosa (PA) can cause infections in compromised hosts by interacting with the glycocalyx of host epithelial cells. It binds to glycostructures on mucosal surfaces via two lectins, which are carbohydrate-binding proteins, named PA-IL and PA-IIL, and blocking this interaction is, thus, an attractive anti-adhesive strategy. The aim of this study was to determine by ciliary beat frequency (CBF) analysis whether monosaccharides or peptides mimicking glycostructures represent blockers of PA lectin binding to human airway cilia. The treatment with monosaccharides and peptides alone did not change the CBF compared to controls and the tested compounds did not influence the cell morphology or survival, with the exception of peptide pOM3. PA-IL caused a decrease of the CBF within 24 h. D-galactose as well as the peptides mimicking HNK-1, polysialic acid and fucose compensated the CBF-modulating effect of PA-IL with different affinities. PA-IIL also bound to the human airway cilia in cell culture and resulted in a decrease of the CBF within 24 h. L(-)-fucose and pHNK-1 blocked the CBF-decreasing effect of PA-IIL. The HNK-1-specific glycomimetic peptide had a high affinity for binding to both PA-IL and PA-IIL, and inhibited the ciliotoxic effect of both lectins, thus, making it a strong candidate for a therapeutic anti-adhesive drug.
AB - Pseudomonas aeruginosa (PA) can cause infections in compromised hosts by interacting with the glycocalyx of host epithelial cells. It binds to glycostructures on mucosal surfaces via two lectins, which are carbohydrate-binding proteins, named PA-IL and PA-IIL, and blocking this interaction is, thus, an attractive anti-adhesive strategy. The aim of this study was to determine by ciliary beat frequency (CBF) analysis whether monosaccharides or peptides mimicking glycostructures represent blockers of PA lectin binding to human airway cilia. The treatment with monosaccharides and peptides alone did not change the CBF compared to controls and the tested compounds did not influence the cell morphology or survival, with the exception of peptide pOM3. PA-IL caused a decrease of the CBF within 24 h. D-galactose as well as the peptides mimicking HNK-1, polysialic acid and fucose compensated the CBF-modulating effect of PA-IL with different affinities. PA-IIL also bound to the human airway cilia in cell culture and resulted in a decrease of the CBF within 24 h. L(-)-fucose and pHNK-1 blocked the CBF-decreasing effect of PA-IIL. The HNK-1-specific glycomimetic peptide had a high affinity for binding to both PA-IL and PA-IIL, and inhibited the ciliotoxic effect of both lectins, thus, making it a strong candidate for a therapeutic anti-adhesive drug.
KW - Humans
KW - Amino Acid Sequence
KW - Molecular Sequence Data
KW - Binding Sites
KW - Bacterial Proteins/metabolism
KW - Adhesins, Bacterial/metabolism
KW - Antigens, CD57/chemistry/metabolism
KW - Bacterial Adhesion/drug effects
KW - Bronchi/metabolism/microbiology
KW - Cilia/drug effects/metabolism
KW - Fucose/chemistry/metabolism
KW - Galactose/chemistry/metabolism
KW - Lectins/antagonists & inhibitors/metabolism
KW - Molecular Mimicry
KW - Monosaccharides/pharmacology
KW - Peptides/chemistry/pharmacology
KW - Pseudomonas aeruginosa/metabolism/pathogenicity
KW - Humans
KW - Amino Acid Sequence
KW - Molecular Sequence Data
KW - Binding Sites
KW - Bacterial Proteins/metabolism
KW - Adhesins, Bacterial/metabolism
KW - Antigens, CD57/chemistry/metabolism
KW - Bacterial Adhesion/drug effects
KW - Bronchi/metabolism/microbiology
KW - Cilia/drug effects/metabolism
KW - Fucose/chemistry/metabolism
KW - Galactose/chemistry/metabolism
KW - Lectins/antagonists & inhibitors/metabolism
KW - Molecular Mimicry
KW - Monosaccharides/pharmacology
KW - Peptides/chemistry/pharmacology
KW - Pseudomonas aeruginosa/metabolism/pathogenicity
M3 - SCORING: Journal article
VL - 31
SP - 207
EP - 215
JO - EUR J CLIN MICROBIOL
JF - EUR J CLIN MICROBIOL
SN - 0934-9723
IS - 2
M1 - 2
ER -
