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Broth Microdilution In Vitro Screening: An Easy and Fast Method to Detect New Antifungal Compounds
Published on: February 14, 2018
Target substances of some antifungal agents in the cell membrane
Abstract:
Copiamycin, an antifungal antibiotic, exhibits antimicrobial activity against a few bacteria in addition to a wide variety of fungi. The methanol extract of Sarcina lutea, one of the most susceptible bacteria, was found to reverse the antimicrobial activity of copiamycin. The reversing activity was associated with the phospholipid fraction of the bacteria. The S. lutea phospholipids also reversed the activities of azalomycin F and miconazole, but not that of clotrimazole. The effects of authentic phospholipids and fatty acids were also investigated. As the antimicrobial activities of copiamycin and azalomycin F were most strongly reversed in the same manner by phospholipids with unsaturated fatty acids and basic hydrophilic groups, the sites on the cell membrane sensitive to both antibiotics are assumed to be identical. On the other hand, the activity of miconazole was affected by different phospholipids from those which affected these two antifungal antibiotics, and the activity of clotrimazole was not affected by any of the phospholipids and fatty acids. It was postulated that the sites on the cell membrane sensitive to miconazole and clotrimazole are different from those sensitive to copiamycin and azalomycin F.
Insights
Bacterial phospholipids, particularly those with unsaturated fatty acids, can reverse the antimicrobial effects of certain antifungal antibiotics like copiamycin and azalomycin F. This suggests shared cellular targets for these drugs.
Area of Science:
- Microbiology
- Biochemistry
- Pharmacology
Background:
- Copiamycin is an antifungal antibiotic with activity against some bacteria.
- Sarcina lutea phospholipids were found to reverse copiamycin's antimicrobial activity.
Purpose of the Study:
- To investigate the reversing activity of Sarcina lutea phospholipids on antimicrobial agents.
- To elucidate the mechanism of action and potential resistance pathways for antifungal drugs.
Main Methods:
- Extraction and fractionation of Sarcina lutea methanol extract.
- Testing the effect of bacterial phospholipids and fatty acids on antibiotic activity.
- Comparative analysis of phospholipid effects on different antifungal agents.
Main Results:
- Sarcina lutea phospholipids reversed the activity of copiamycin, azalomycin F, and miconazole, but not clotrimazole.
- Phospholipids with unsaturated fatty acids and basic hydrophilic groups most effectively reversed copiamycin and azalomycin F activity.
- Miconazole activity was affected by different phospholipids, while clotrimazole was unaffected.
Conclusions:
- Copiamycin and azalomycin F likely share identical cell membrane target sites.
- Miconazole and clotrimazole appear to interact with different cell membrane sites compared to copiamycin and azalomycin F.
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