Affiliation:
1. Cambridge Centre for Molecular Recognition, University Chemical Laboratory, England.
Abstract
The association of vancomycin group antibiotics with the growing bacterial cell wall was investigated by using the cell wall precursor analog di-N-acetyl-Lys-D-Ala-D-Ala in competition binding experiments. The affinities of the antibiotics for the -D-Ala-D-Ala-containing cell wall precursors of Bacillus subtilis ATCC 6633 (a model for vancomycin-susceptible gram-positive bacteria) and for the -D-Ala-D-Lac-containing cell wall precursors of Leuconostoc mesenteroides (a model for vancomycin-resistant strains of Enterococcus faecium and Enterococcus faecalis) were determined by a whole-cell assay. The binding of strongly dimerizing antibiotics such as eremomycin to the bacterial surface was thus shown to be enhanced by up to 2 orders of magnitude (relative to the binding in free solution) by the chelate effect, whereas weakly dimerizing antibiotics like vancomycin and antibiotics carrying lipid tails (teicoplanin) benefited less (ca. 1 order of magnitude). The affinity measured in this way correlates well with the MIC of the antibiotic, and a consequence of this is that future design of semisynthetic vancomycin-group antibiotics should attempt to incorporate chelate effect-enhancing structural features.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
37 articles.
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