Correlation between lipopolysaccharide structure and permeability resistance in beta-lactam-resistant Pseudomonas aeruginosa.
Four beta-lactam-resistant permeability mutants of Pseudomonas aeruginosa PAO503 were studied. The resistance phenotypes were correlated to changes within the lipopolysaccharide. Two of the mutants, PCC1 and PCC19, were shown to differentiate between beta-lactams on the basis of relative hydrophobicity. The more hydrophilic antibiotics were less effective at inhibiting these strains. This phenotype was correlated to the presence of mannose, in measurable quantities, in lipopolysaccharide isolated from these strains. The other two strains, PCC23 and PCC100, differentiated between cephem antibiotics on the basis of electrical charge. The presence of a positive charge markedly increased the relative efficiency of an antibiotic. This correlation did not hold for penam derivatives, with the lower-molecular-weight, dianionic molecules being the most effective. Mutants of this type were changed in the amount of "side chain" sugars or, to minor extent, in their outer membrane protein profiles.
D000596:Amino Acids / Q000032:analysis; D000606:Amino Sugars / Q000032:analysis; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000032:analysis; D002463:Cell Membrane Permeability; D004352:Drug Resistance, Microbial; D004591:Electrophoresis, Polyacrylamide Gel; D006602:Hexosyltransferases; D008070:Lipopolysaccharides / Q000032:analysis*; D002267:Muramoylpentapeptide Carboxypeptidase / Q000032:analysis; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000378:metabolism; D047090:beta-Lactams
D000596:Amino Acids; D000606:Amino Sugars; D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D008070:Lipopolysaccharides; D046915:Penicillin-Binding Proteins; D047090:beta-Lactams; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase