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Oxacillin-induced lysis of Staphylococcus aureus
Antimicrobial Agents and Chemotherapy
|August 1, 1979
Summary
Oxacillin tolerance in Staphylococcus aureus (S. aureus) is linked to reduced cell lysis and increased secretion of lipoteichoic acid. This suggests lipoteichoic acid may inhibit autolysins, contributing to antibiotic tolerance.
Area of Science:
- Microbiology
- Antibiotic Resistance
- Molecular Biology
Background:
- Staphylococcus aureus exhibits varying susceptibility to oxacillin.
- Oxacillin tolerance is characterized by a discrepancy between bacteriostatic and bactericidal concentrations.
- Understanding the mechanisms of antibiotic tolerance is crucial for effective treatment.
Purpose of the Study:
- To investigate the mechanisms underlying oxacillin tolerance in clinical isolates of Staphylococcus aureus.
- To compare the lytic response and cellular behavior of oxacillin-tolerant (Tol(+)) and non-tolerant (Tol(-)) strains.
- To identify potential factors involved in oxacillin tolerance.
Main Methods:
- Comparison of minimum bactericidal and bacteriostatic concentrations for oxacillin against six S. aureus clinical isolates.
- Analysis of lysis curves and viability loss in response to oxacillin inhibition.
- Measurement of [(14)C]glycerol uptake and secretion.
- Characterization of secreted material using SDS-PAGE and Sepharose 6B chromatography.
- Testing the effect of secreted material on the lytic response of Tol(-) strains.
Main Results:
- Tol(+) strains showed significantly higher minimum bactericidal concentrations compared to minimum bacteriostatic concentrations, indicating tolerance.
- Tol(+) strains exhibited a diminished rate of lysis and viability loss when exposed to oxacillin.
- Tol(+) strains released over twice the amount of radiolabeled glycerol compared to Tol(-) strains.
- Lipoteichoic acid was identified as the major component of the secreted material.
- Addition of lipoteichoic acid to oxacillin-inhibited Tol(-) strains inhibited their lytic response.
Conclusions:
- Oxacillin tolerance in S. aureus is associated with reduced autolysis and increased secretion of lipoteichoic acid.
- Lipoteichoic acid may function as an autolysin inhibitor, contributing to oxacillin tolerance.
- These findings provide insights into the molecular mechanisms of antibiotic tolerance in S. aureus.