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Teicoplanin stress-selected mutations increasing sigma(B) activity in Staphylococcus aureus
1Institute of Medical Microbiology, University of Zürich, CH8028 Zürich, Switzerland. bischoff@immv.unizh.ch
Antimicrobial Agents and Chemotherapy
|May 17, 2001
Summary
Staphylococcus aureus teicoplanin resistance is linked to increased activity of the transcription factor sigma(B). Mutations in the sigB operon, not pigment production, drive this resistance, suggesting sigma(B)-controlled genes are key.
Area of Science:
- Microbiology
- Molecular Biology
- Genetics
Background:
- Staphylococcus aureus uses the RsbU pathway to activate the alternative transcription factor sigma(B).
- A natural rsbU mutant exhibits unpigmented colonies due to impaired sigma(B) activation.
- Teicoplanin resistance is a significant clinical concern in S. aureus infections.
Purpose of the Study:
- To investigate the mechanism of teicoplanin resistance development in Staphylococcus aureus.
- To determine the role of sigma(B) activity and pigment production in teicoplanin resistance.
- To identify genetic mutations associated with increased teicoplanin resistance.
Main Methods:
- Selection of teicoplanin-resistant mutants from an rsbU mutant strain.
- Utilizing an asp23 promoter-luciferase fusion to measure sigma(B) activity.
- Genetic analysis of mutations within the sigB operon and the crtM gene.
Main Results:
- Teicoplanin-resistant mutants predominantly displayed intense orange pigmentation and increased sigma(B) activity.
- Increased sigma(B) activity resulted from mutations in rsbW or its promoter, enhancing the sigma(B)/RsbW ratio.
- Mutations within the sigB operon correlated with teicoplanin resistance, while carotenoid production (crtM gene) was not essential for resistance.
Conclusions:
- Upregulation of sigma(B) activity is implicated in the development of teicoplanin resistance in S. aureus.
- Sigma(B)-controlled genes likely play a direct or indirect role in mediating teicoplanin resistance.
- Carotenoids do not contribute to teicoplanin resistance in this context.