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Effects of antimutagens on development of drug/antibiotic resistance in microorganisms
1University of Kansas, Department of Microbiology, Lawrence, KS 66045, USA.
Abstract:
The effects of polyamines and related compounds on the development of drug/antibiotic resistance in a variety of bacterial strains were studied. Methods employed included standard toxicity assays, modified Ames tests for mutation frequencies and antimutagenic effects, prophage induction assays, and recA-lacZ and ada-lacZ induction assays. Using these methods, we have shown that the polyamines produce strong antimutagenic effects against EMS and MMS-induced antibiotic resistance. Spermidine also seems to have antimutagenic potential against 4NQO-induced mutations. DNA fidelity assays suggest that polyamines play a vital role in DNA synthesis, and several polyamines prevent the development of resistance to dihydrostreptomycin. The polyamine putrescine appears to be required for streptomycin action and also enhances the activity of some antibiotics (e.g., neomycin, kanamycin) but shows no enhancing effect on tetracycline or erythromycin. The potential significance of these studies for infectious diseases and tumor therapy is discussed.
Insights
Polyamines significantly inhibit antibiotic resistance development in bacteria by acting as antimutagens and supporting DNA synthesis. Certain polyamines like putrescine also modulate the efficacy of specific antibiotics.
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Background:
- Bacterial antibiotic resistance is a growing global health threat.
- Polyamines are essential molecules involved in various cellular processes, including DNA replication and stability.
Purpose of the Study:
- To investigate the role of polyamines in the development of bacterial drug and antibiotic resistance.
- To assess the antimutagenic and DNA fidelity effects of polyamines.
Main Methods:
- Standard toxicity assays.
- Modified Ames tests for mutation frequency and antimutagenic effects.
- Prophage induction, recA-lacZ, and ada-lacZ induction assays.
- DNA fidelity assays.
Main Results:
- Polyamines demonstrated strong antimutagenic effects against ethyl methanesulfonate (EMS) and methyl methanesulfonate (MMS)-induced antibiotic resistance.
- Spermidine showed antimutagenic potential against 4-nitroquinoline 1-oxide (4NQO)-induced mutations.
- Polyamines are crucial for DNA synthesis fidelity and prevent resistance to dihydrostreptomycin.
- Putrescine is required for streptomycin action and enhances neomycin and kanamycin activity.
Conclusions:
- Polyamines play a significant role in preventing the emergence of antibiotic resistance in bacteria.
- Understanding polyamine-antibiotic interactions could offer new therapeutic strategies for infectious diseases and cancer.