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Abstract:
Lomofungin inhibited the growth of some yeasts and mycelial fungi at concentrations between 5 and 10 mug/ml. At such concentrations, there was no decrease in endogenous and exogenous oxygen consumption, and even 50 mug of antibiotic per ml caused only slight decreases. The permeation of the cell membrane was changed so that leakage of ninhydrin-positive substances was reduced, and the uptake of (14)C-labeled glucose, amino acids, uracil, and thymidine was decreased at concentrations as low as 4 mug/ml. Protein synthesis in whole cells of Saccharomyces cerevisiae was reduced 35% at 10 mug/ml. However, the antibiotic did not reduce the incorporation of phenylalanine-U-(14)C into polypeptides with cell-free systems of Rhizoctonia solani and S. cerevisiae. The synthesis of ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) was inhibited even at concentrations of lomofungin of 4 mug/ml. Since RNA synthesis was inhibited at lower concentrations and earlier than DNA synthesis, the primary site of action of the antibiotic appears to be the synthesis of RNA.
Insights
Lomofungin, an antifungal agent, inhibits fungal growth by affecting nutrient uptake and nucleic acid synthesis. Its primary action appears to be the inhibition of ribonucleic acid (RNA) synthesis in fungi.
Area of Science:
- Mycology
- Biochemistry
- Antimicrobial Research
Background:
- Fungal infections pose significant health challenges.
- Novel antifungal agents are crucial for combating drug-resistant fungal strains.
- Understanding the mechanism of action of existing antifungals can guide the development of new therapies.
Purpose of the Study:
- To investigate the mechanism of action of the antifungal agent lomofungin.
- To determine the effects of lomofungin on fungal growth, cell membrane permeability, and macromolecular synthesis.
Main Methods:
- Assessing fungal growth inhibition in yeasts and mycelial fungi.
- Measuring oxygen consumption in fungal cells.
- Evaluating the uptake of radiolabeled nutrients and the synthesis of proteins, RNA, and DNA.
Main Results:
- Lomofungin inhibited fungal growth at 5-10 µg/ml.
- It altered cell membrane permeability, reducing leakage and nutrient uptake.
- RNA and DNA synthesis were inhibited at 4 µg/ml, with RNA synthesis being more sensitive.
Conclusions:
- Lomofungin's antifungal activity is linked to impaired nutrient uptake and nucleic acid synthesis.
- The primary site of action is likely the inhibition of RNA synthesis.
- Further research into lomofungin could lead to new antifungal strategies.