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Bactericidal Action of 2-Hydroxy-3-(Cyclohexylpropyl)-1,4-Naphthoquinone on Bacillus megaterium

¹ Department of Molecular Biology, Walter Reed Army Institute of Research, Washington, D.C. 20012, and Microbiology Department, University of Maryland, College Park, Maryland 20742

ABSTRACT

The antimalarial drug, 2-hydroxy-3-(cyclohexylpropyl)-1,4-naphthoquinone (NQ), at concentrations of approximately 10^–5M (3 µg/ml), was bactericidal for the gram-positive bacterium, Bacillus megaterium. Only a few other gram-positive bacteria were sensitive to this drug. All growth inhibitory concentrations of NQ were also bactericidal for B. megaterium, and even resting suspensions of cells were killed. The incorporation of radioactive-labeled leucine, thymidine, uracil, and diaminopimelic acid into protein, deoxyribonucleic acid, ribonucleic acid, and the cell wall polymer was arrested immediately and completely upon addition of NQ to cultures in exponential growth. NQ produced a delayed effect on aerobic respiration and no change in the rate of oxygen consumption was observed at a time when all major biosyntheses had failed. ³H-NQ was demonstrated to bind strongly and preferentially to the bacterial cell membrane. This simultaneous shutdown of all major categories of in vivo macromolecular syntheses points to an effect of NQ upon membrane-centered energy supplying reactions or transport of essential nutrients, or both.