Involvement of outer membrane of Pseudomonas cepacia in aminoglycoside and polymyxin resistance.
Pseudomonas cepacia was found to be resistant to the outer membrane-permeabilizing effects of aminoglycoside antibiotics, polymyxin B, and EDTA. Permeabilization of P. cepacia to the fluorescent probe 1-N-phenylnaphthylamine was not achieved at concentrations 100- to 1,000-fold above those required to permeabilize Pseudomonas aeruginosa. Furthermore, in contrast to P. aeruginosa cells, intact cells of P. cepacia did not bind the fluorescent probe dansyl-polymyxin. However, purified lipopolysaccharide (LPS) from P. cepacia bound dansyl-polymyxin with approximately the same affinity as did LPS from P. aeruginosa. Also, binding of dansyl-polymyxin to P. cepacia (and P. aeruginosa) LPS was inhibited by polymyxin B, streptomycin, gentamicin, and Mg2+. These data suggest that P. cepacia does not utilize the self-promoted pathway for aminoglycoside uptake and that the outer membrane is arranged in a way that conceals or protects cation-binding sites on LPS which are capable of binding polycations such as aminoglycosides or polymxyin.
D000617:Aminoglycosides / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects*; D004352:Drug Resistance, Microbial; D004492:Edetic Acid / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008070:Lipopolysaccharides / Q000378:metabolism; D011112:Polymyxin B / Q000378:metabolism / Q000494:pharmacology*; D011113:Polymyxins / Q000494:pharmacology*; D011549:Pseudomonas / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000648:ultrastructure
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D008070:Lipopolysaccharides; D011113:Polymyxins; D004492:Edetic Acid; D011112:Polymyxin B