Lipopolysaccharide alterations responsible for combined quinolone and beta-lactam resistance in Pseudomonas aeruginosa.
Resistant variants of three clinical Pseudomonas aeruginosa isolates were obtained in the presence of aztreonam. The variants exhibited a four- to eightfold increase in the minimal inhibitory concentrations to beta-lactam antibiotics (except imipenem) to quinolones, such as norfloxacin and fleroxacin, chloramphenicol and tetracycline, but not to gentamicin and polymyxin B. beta-Lactamase production was barely detectable in both wild-type strains and the resistant clones. Only ampicillin, cefoxitin and imipenem increased the production of beta-lactamase, whereas various other beta-lactams did not. Penicillin-binding proteins remained unchanged in the aztreonam-resistant clones. The analysis of the outer membrane proteins did not reveal differences in the outer membrane proteins between the wild-type strains and the aztreonam-resistant clones. Two of the three antibiotic-resistant isogenic clones contained less lipopolysaccharides (LPSs) than their corresponding wild-type strains. Moreover, it could be demonstrated that the ratio of 2-keto-3-deoxy octonate to carbohydrate of the LPS changed in any case between the wild-type strains and the aztreonam-resistant clones. These alterations were accompanied by a decrease in surface hydrophobicity of the resistant clones as compared to the wild-type strains. Therefore, quantitative as well as qualitative alterations in the LPS may provide an explanation for the resistant phenotype observed.
Leying
H J
HJ
Department of Medical Microbiology, Ruhr University, Bochum, FRG.
Büscher
K H
KH
Cullmann
W
W
Then
R L
RL
D042462:4-Quinolones; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000032:analysis; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000032:analysis; D004352:Drug Resistance, Microbial; D006602:Hexosyltransferases; D008070:Lipopolysaccharides / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D002267:Muramoylpentapeptide Carboxypeptidase / Q000032:analysis; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D011550:Pseudomonas aeruginosa / Q000201:enzymology / Q000378:metabolism*; D013329:Structure-Activity Relationship; D001618:beta-Lactamases / Q000096:biosynthesis; D047090:beta-Lactams
D042462:4-Quinolones; D000900:Anti-Bacterial Agents; D000890:Anti-Infective 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; D001618:beta-Lactamases