Effects of antimutagens on development of drug/antibiotic resistance in microorganisms.
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.
Pillai
S P
SP
University of Kansas, Department of Microbiology, Lawrence, KS 66045, USA.
Shankel
D M
DM
D016587:Antimutagenic Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D004352:Drug Resistance, Microbial / Q000235:genetics; D029968:Escherichia coli Proteins; D007763:Lac Operon; D009152:Mutagenicity Tests; D019853:O(6)-Methylguanine-DNA Methyltransferase; D011073:Polyamines / Q000494:pharmacology*; D011938:Rec A Recombinases / Q000235:genetics; D012270:Ribosomes; D012486:Salmonella typhimurium / Q000235:genetics; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D014157:Transcription Factors
D016587:Antimutagenic Agents; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D011073:Polyamines; D014157:Transcription Factors; C045675:Ada protein, E coli; D019853:O(6)-Methylguanine-DNA Methyltransferase; D011938:Rec A Recombinases