Abstract
Oxolinic acid (1-ethyl-1,4-dihydro-6,7-methylenedioxy-4-oxo-3-quinolinecarboxylic acid) is an antimicrobial agent effective against a variety of gram-negative pathogens, including Proteus. With the exception of Staphylococcus aureus, oxolinic acid is inactive against gram-positive bacteria and against fungi. Our results suggest that oxolinic acid exerted its primary action on synthesis of deoxyribonucleic acid (DNA). The rate of thymidine-2-(14)C incorporation into DNA was significantly depressed in the presence of 0.1 mug of oxolinic acid per ml and was markedly inhibited at 1 mug/ml. No evidence of complexing with DNA was observed. Pulse labeling with radioactive precursors revealed that at levels approximating the minimal inhibitory concentration, oxolinic acid had no effect on rate of incorporation of (14)C-valine into protein, uracil-2-(14)C into ribonucleic acid, or sodium acetate-1-(14)C into lipid. Filamentous forms of P. vulgaris ATCC 881 were observed after in vitro exposure to subinhibitory levels of oxolinic acid. Concentrations of oxolinic acid in excess of the minimal inhibitory concentration (0.39 mug/ml) did not cause lysis of cells of P. vulgaris or leakage of cytoplasmic materials. Mg(++) ions diminished the in vitro activity of oxolinic acid, possibly through formation of Mg(++) chelates
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