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Permeability to beta-lactams in Bacteroides fragilis
G J Cuchural1, S Hurlbut, M H Malamy
1Department of Pathology, New England Medical Center Hospital, Boston, Massachusetts.
The Journal of Antimicrobial Chemotherapy
|December 1, 1988
Summary
Bacteroides fragilis outer membrane permeability to beta-lactam antibiotics was investigated. Increased drug hydrophobicity enhanced uptake, unlike in Escherichia coli, suggesting unique transport mechanisms for these critical antimicrobial agents.
Area of Science:
- Microbiology
- Pharmacology
- Biochemistry
Background:
- Bacteroides fragilis is an important opportunistic pathogen.
- Understanding outer membrane permeability is crucial for developing effective antimicrobial therapies.
- Beta-lactamases in B. fragilis hydrolyze most beta-lactam antibiotics.
Purpose of the Study:
- To assess the outer membrane permeability of Bacteroides fragilis strains to various beta-lactam compounds.
- To elucidate the physicochemical factors influencing beta-lactam drug uptake by B. fragilis.
Main Methods:
- Utilized Bacteroides fragilis strains TAL2480 and TAL3636, possessing broad-spectrum beta-lactamases.
- Determined outer membrane permeability using the Zimmerman & Rosselet method (1977).
- Analyzed the influence of ionic charge, hydrophobicity, and molecular weight on drug uptake.
Main Results:
- Established a rank order of permeative ability for tested beta-lactams, with cephaloridine showing the highest and latamoxef the lowest.
- Identified ionic charge, hydrophobicity, and molecular weight as key determinants of beta-lactam uptake.
- Observed that increased hydrophobicity correlated with increased drug uptake in B. fragilis, contrasting with Escherichia coli findings.
Conclusions:
- Outer membrane permeability in B. fragilis is influenced by drug physicochemical properties.
- B. fragilis exhibits distinct drug uptake characteristics compared to E. coli, particularly regarding hydrophobicity.
- These findings have implications for designing novel beta-lactam antibiotics effective against B. fragilis infections.