Impaired imipenem uptake associated with alterations in outer membrane proteins and lipopolysaccharides in imipenem-resistant Shigella dysenteriae

Three imipenem-resistant mutants were obtained from a clinical isolate (C152) of Shigella dysenteriae by selection with increasing concentrations of imipenem. Resistance to imipenem was associated with resistance to several other beta-lactam antibiotics. The penicillin-binding protein (PBP) patterns...

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Bibliographic Details
Published in:Journal of antimicrobial chemotherapy 1999-02, Vol.43 (2), p.195-201
Main Authors: ANINDYA SUNDAR GHOSH, ALAK KANTI KAR, KUNDU, M
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - pharmacology
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
Bacterial Outer Membrane Proteins - drug effects
Bacterial Outer Membrane Proteins - metabolism
Bacterial Proteins
Biological and medical sciences
Carrier Proteins - metabolism
Drug Resistance, Microbial
Hexosyltransferases
Imipenem - pharmacokinetics
Imipenem - pharmacology
Lipopolysaccharides - metabolism
Medical sciences
Microbial Sensitivity Tests
Muramoylpentapeptide Carboxypeptidase - metabolism
Mutation
Penicillin-Binding Proteins
Peptidyl Transferases
Pharmacology. Drug treatments
Shigella dysenteriae - drug effects
Shigella dysenteriae - genetics
Shigella dysenteriae - metabolism
Thienamycins - pharmacokinetics
Thienamycins - pharmacology
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Summary:Three imipenem-resistant mutants were obtained from a clinical isolate (C152) of Shigella dysenteriae by selection with increasing concentrations of imipenem. Resistance to imipenem was associated with resistance to several other beta-lactam antibiotics. The penicillin-binding protein (PBP) patterns of the resistant and the wild-type strains were comparable. The permeability of the outer membrane proteins (OMPs) of the most resistant mutant, IM16, was lower than that of the parent strain C152 when imipenem and arabinose were used as test solutes. This mutant had lower levels of both the major OMPs of M(r) 43,000 and 38,000. There were also differences in the patterns of lipopolysaccharide (LPS) of the mutants and the wild-type strain. The mutant IM16 had less short-chain LPS than the parent C152. Increasing imipenem resistance was also associated with a concomitant decrease in the level of 2-keto-3-deoxyoctonate, a component of the core region of LPS.
ISSN:0305-7453
1460-2091
1460-2091
DOI:10.1093/jac/43.2.195