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Antibacterial agents and release of periplasmic pertussis toxin from Bordetella pertussis
1Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, Cincinnati, Ohio 45267-0524, USA.
Abstract:
Pertussis toxin accumulates in the periplasm of Bordetella pertussis prior to secretion, and we examined its fate following treatment with antimicrobial agents. Both antibiotics that inhibit protein synthesis (erythromycin and chloramphenicol), transcription (rifampin), or cell wall biosynthesis (cefoperazone and piperacillin) and magnesium sulfate (which inhibits transcription of pertussis toxin, but not bacterial growth) did not prevent release of preformed toxin. In contrast, agents that affect bacterial membranes, such as polymyxin B, lidocaine, procaine, and ethanol, inhibited release of preformed pertussis toxin. These results suggest new protein synthesis is not required for pertussis toxin secretion, but a functional membrane complex is required.
Insights
Antimicrobial agents targeting bacterial membranes, not protein synthesis or transcription, inhibited pertussis toxin release from Bordetella pertussis. This suggests membrane integrity is crucial for toxin secretion.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Molecular Biology
Background:
- Pertussis toxin is a key virulence factor secreted by Bordetella pertussis.
- The toxin accumulates in the periplasm before secretion.
- Understanding the secretion mechanism is vital for developing targeted therapies.
Purpose of the Study:
- To investigate the effects of various antimicrobial agents on the release of preformed pertussis toxin.
- To determine the role of protein synthesis, transcription, and membrane integrity in toxin secretion.
Main Methods:
- Bordetella pertussis cultures were treated with antibiotics inhibiting protein synthesis (erythromycin, chloramphenicol), transcription (rifampin), cell wall biosynthesis (cefoperazone, piperacillin), or magnesium sulfate.
- The impact of membrane-affecting agents (polymyxin B, lidocaine, procaine, ethanol) on toxin release was assessed.
Main Results:
- Antibiotics targeting protein synthesis, transcription, or cell wall biosynthesis did not prevent pertussis toxin release.
- Magnesium sulfate inhibited toxin gene transcription but not the release of preformed toxin.
- Agents disrupting bacterial membranes significantly inhibited the release of preformed pertussis toxin.
Conclusions:
- New protein synthesis is not required for the secretion of preformed pertussis toxin.
- A functional bacterial membrane complex is essential for the release of pertussis toxin.
- Targeting bacterial membrane integrity may represent a novel strategy to inhibit pertussis toxin secretion.