Decreased binding of antibiotics to lipopolysaccharides from polymyxin-resistant strains of Escherichia coli and Salmonella typhimurium.
The interactions of polycationic antibiotics with lipopolysaccharide (LPS) isolated from parental and polymyxin-resistant strains of Salmonella typhimurium and Escherichia coli were measured by using a cationic spin probe. Electron spin resonance spectra indicated that increasing concentrations of cations competitively displaced probe from LPS aggregates. Polymyxin B and other cations displaced less probe from LPS of polymyxin-resistant strains than from LPS of the parental strains, whereas the same amount or more probe was displaced from isolates of the mutants by the structurally similar antibiotic, EM 49 (octapeptin). In general, the differential affinities of these antibiotics for LPS correlated with their antibiotic activity in vivo, suggesting that resistance results from a decrease in antibiotic permeability across the outer membrane due to alterations in the LPS which affect antibiotic binding. The alterations in the structure of LPS from the polymyxin-resistant mutants of E. coli were characterized using 31P nuclear magnetic resonance spectroscopy. The results suggested that esterification of the core-lipid A phosphates is responsible for increased resistance to polymyxin B and that this alteration is different from that previously proposed for the S. typhimurium strains. In both cases, however, resistance was the result of modifications that result in a less acidic lipid A.
D000900:Anti-Bacterial Agents / Q000378:metabolism*; D004352:Drug Resistance, Microbial; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism*; D055666:Lipopeptides; D008070:Lipopolysaccharides / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D009842:Oligopeptides / Q000378:metabolism; D010455:Peptides; D010456:Peptides, Cyclic / Q000378:metabolism; D011112:Polymyxin B / Q000378:metabolism* / Q000494:pharmacology; D011113:Polymyxins / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D055666:Lipopeptides; D008070:Lipopolysaccharides; D009842:Oligopeptides; D010455:Peptides; D010456:Peptides, Cyclic; D011113:Polymyxins; C013629:octapeptin antibiotics; D011112:Polymyxin B