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PDBsum entry 5d2a
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Sugar binding protein
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PDB id
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5d2a
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References listed in PDB file
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Key reference
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Title
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Overcoming antibiotic resistance in pseudomonas aeruginosa biofilms using glycopeptide dendrimers.
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Authors
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G.Michaud,
R.Visini,
M.Bergmann,
G.Salerno,
R.Bosco,
E.Gillon,
B.Richichi,
C.Nativi,
A.Imberty,
A.Stocker,
T.Darbre,
J.L.Reymond.
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Ref.
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Chem Sci, 2016,
7,
166-182.
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PubMed id
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Abstract
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Antibiotic resistance in the opportunistic pathogen Pseudomonas
aeruginosa is partly caused by biofilms forming a physical barrier to
antibiotic penetration. Here we focused on modifying tetravalent glycopeptide
dendrimer ligands of P. aeruginosa lectins LecB or LecA to increase their
biofilm inhibition activity. First heteroglycoclusters were investigated
displaying one pair each of LecB specific fucosyl groups and LecA specific
galactosyl groups and binding simultaneously to both lectins, one of which gave
the first fully resolved crystal structure of a peptide dendrimer as LecB
complex providing a structural model for dendrimer-lectin interactions (PDB ;
5D2A). Biofilm inhibition was increased by introducing additional cationic
residues in these dendrimers but resulted in bactericidal effects similar to
those of non-glycosylated polycationic antimicrobial peptide dendrimers. In a
second approach dendrimers displaying four copies of the natural LecB ligand
Lewisa were prepared leading to slightly stronger LecB binding and
biofilm inhibition. Finally synergistic application of a LecB specific
non-bactericidal antibiofilm dendrimer with the antibiotic tobramycin at
sub-inhibitory concentrations of both compounds allowed effective biofilm
inhibition and dispersal.
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