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Interaction of divalent cations, quinolones and bacteria
1Department of Infection, Medical School, University of Birmingham, UK.
The Journal of Antimicrobial Chemotherapy
|October 1, 1994
Summary
Divalent cations like magnesium and calcium reduce the effectiveness of quinolone antibiotics. This occurs because cations bind to quinolones, decreasing their accumulation in bacteria and potentially affecting their interaction with DNA gyrase.
Area of Science:
- Microbiology
- Pharmacology
- Biochemistry
Background:
- Quinolones are a class of antibiotics crucial for treating bacterial infections.
- Divalent cations are known to influence the activity of various antimicrobial agents.
Purpose of the Study:
- To investigate the interaction between divalent cations and quinolones.
- To elucidate the mechanism by which divalent cations antagonize quinolone antimicrobial activity.
Main Methods:
- Minimum inhibitory concentration (MIC) assays with 18 quinolones in the presence of magnesium or calcium chloride.
- Bacterial accumulation studies and DNA synthesis inhibition assays.
- Fluorescence assays to detect quinolone-magnesium chelation.
- Thin layer chromatography to analyze quinolone-magnesium complexes.
Main Results:
- Magnesium and calcium chloride increased quinolone MICs against Gram-positive and Gram-negative bacteria.
- Magnesium chloride decreased quinolone accumulation and DNA synthesis inhibition.
- Fluorescence assays confirmed magnesium chelation of quinolones, with varying enhancement.
- Thin layer chromatography suggested a 1:1 complex ratio, ruling out steric hindrance via porin channels.
Conclusions:
- Divalent cations antagonize quinolone activity likely through chelation, reducing drug availability within bacteria.
- This chelation may involve exogenous ions or ions associated with bacterial cell wall components.
- An alternative mechanism involves a direct effect on the quinolone-DNA gyrase interaction.