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STUDIES ON THE ANTIBACTERIAL ACTION OF THE SULFONAMIDE DRUGS : II. THE POSSIBLE RELATION OF DRUG ACTIVITY TO
1Biological Division of the Department of Medicine, Johns Hopkins University Medical School, Baltimore.
The Journal of Experimental Medicine
|October 30, 2009
Summary
Nicotinamide and cozymase block sulfonamide drugs in Staphylococcus aureus cultures. Their antagonistic effect is linked to growth stimulation, not coenzyme interference, challenging existing theories on sulfonamide action.
Area of Science:
- Microbiology
- Biochemistry
- Pharmacology
Background:
- Sulfonamide drugs are widely used antibacterials.
- Their precise mechanism of action, particularly regarding coenzyme interactions, remains debated.
- Previous theories suggested sulfonamides interfere with coenzymes like cozymase.
Purpose of the Study:
- To investigate the interaction between sulfonamide drugs and coenzymes (cozymase, cocarboxylase) in bacterial cultures.
- To determine if nicotinamide and cozymase antagonize sulfonamide activity.
- To elucidate the mechanism of sulfonamide bacteriostatic action.
Main Methods:
- Bacterial cultures of Staphylococcus aureus and Bacillus coli were used.
- The effect of nicotinamide and cozymase on sulfonamide bacteriostasis was assessed.
- Quantitative studies and Warburg respirometry were employed to measure drug and coenzyme interactions.
Main Results:
- Nicotinamide and cozymase blocked the bacteriostatic action of sulfonamides and organic dyes in S. aureus.
- This antagonism was proportional to the growth-stimulating ability of nicotinamide and cozymase.
- Cocarboxylase activity was unaffected by sulfathiazole in vitro.
- No significant difference in antagonism was observed between cozymase and structurally dissimilar sulfonamides.
Conclusions:
- The findings do not support the theory that sulfonamides inhibit bacterial growth by interfering with cozymase or cocarboxylase.
- The observed antidrug effects are likely related to growth stimulation rather than direct coenzyme antagonism.
- A new perspective on sulfonamide mechanism of action is proposed, explaining variations in potency.
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