INTERACTIONS OF PLAUNOTOL WITH BACTERIAL-MEMBRANES

Plaunotol, a cytoprotective antiulcer agent, has a bactericidal effect against Helicobacter pylori, which may result from interaction of thi s compound with the bacterial cell membrane. The purpose of the presen t study was to confirm that plaunotol interacts with the H. pylori mem brane. Membrane fluidities were measured using two stearic acid spin l abels, namely 5-doxyl-stearic acid (in which the nitroxide group is lo cated in the upper portion of the bacterial cell membrane) and 16-doxy l-stearic acid methyl ester (in which the nitroxide group is located d eeper in the bacterial cell membrane), by means of electron spin reson ance. The membrane fluidities of plaunotol-treated cells were signific antly increased in the measurements made using the two spin labels. We also attempted to isolate plaunotol-resistant H. pylori in vitro by t wo different methods. To assess the level of resistance that could be reached, H. pylori was passaged five times on an agar plate containing subinhibitory concentrations of plaunotol or metronidazole. To measur e the rate of development of resistance, H. pylori was grown with subi nhibitory concentrations (0.25 x MIG) of plaunotol or metronidazole, a nd quantitatively plated on to medium containing 4 x MIC of the compou nds. This treatment was repeated once more. No plaunotol-resistant col onies were selected by the two methods. H. pylori developed resistance to metronidazole easily and at a relatively high rate. The mechanism by which plaunotol directly fluidizes and destroys the H. pylori membr ane might make it difficult for this organism to develop resistance to plaunotol. It was confirmed that the bactericidal effects of plaunoto l were also shown against Staphylococcus aureus, Streptococcus pneumon iae, Neisseria gonorrhoeae, Moraxella catarrhalis and Haemophilus infl uenzae. No such effect was seen against Escherichia coil and Pseudomon as aeruginosa.