PMID:8152392
| Citation |
Howard, BM, Pinney, RJ and Smith, JT (1994) Antagonism between bactericidal activities of 4-quinolones and coumarins gives insight into 4-quinolone killing mechanisms. Microbios 77:121-31 |
|---|---|
| Abstract |
At concentrations exceeding their MICs, novobiocin and coumermycin antagonised the bactericidal activities of nalidixic acid, ciprofloxacin, ofloxacin and norfloxacin against Escherichia coli KL16. The sensitivities to killing by ciprofloxacin of four mutant derivatives of KL16 carrying gyrA, nalB, nal24 or nal31 alleles were also antagonised by novobiocin. The activities of drug combinations were tested in nutrient broth, which allowed expression of 4-quinolone killing mechanisms A, B and C. They were also tested in nutrient broth plus rifampicin to inhibit mechanisms A and C of the 4-quinolones, and in phosphate-buffered saline, which inhibited mechanism A. Results showed that novobiocin antagonised mechanism C, but not B, of both ciprofloxacin and ofloxacin, but did not antagonise mechanism C of norfloxacin. A review of these and other data indicates that mechanism B may result from the activities of SOS error-prone DNA repair on an irreversibly-bound drug-gyrase-DNA complex, and that mechanism C is mediated via drug interaction with the B subunit of DNA gyrase. |
| Links | |
| Keywords |
Aminocoumarins; Anti-Infective Agents/antagonists & inhibitors; Anti-Infective Agents/pharmacology; Ciprofloxacin/antagonists & inhibitors; Ciprofloxacin/pharmacology; Coumarins/pharmacology; DNA Topoisomerases, Type II/chemistry; DNA Topoisomerases, Type II/drug effects; DNA Topoisomerases, Type II/genetics; Escherichia coli/drug effects; Escherichia coli/enzymology; Escherichia coli/genetics; Genes, Bacterial/genetics; Microbial Sensitivity Tests; Mutation; Nalidixic Acid/antagonists & inhibitors; Nalidixic Acid/pharmacology; Norfloxacin/antagonists & inhibitors; Norfloxacin/pharmacology; Novobiocin/pharmacology; Ofloxacin/antagonists & inhibitors; Ofloxacin/pharmacology; Rifampin/pharmacology |
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