Interactions of plaunotol with bacterial membranes.
Plaunotol, a cytoprotective antiulcer agent, has a bactericidal effect against Helicobacter pylori, which may result from interaction of this compound with the bacterial cell membrane. The purpose of the present study was to confirm that plaunotol interacts with the H. pylori membrane. Membrane fluidities were measured using two stearic acid spin labels, namely 5-doxyl-stearic acid (in which the nitroxide group is located in the upper portion of the bacterial cell membrane) and 16-doxyl-stearic acid methyl ester (in which the nitroxide group is located deeper in the bacterial cell membrane), by means of electron spin resonance. The membrane fluidities of plaunotol-treated cells were significantly increased in the measurements made using the two spin labels. We also attempted to isolate plaunotol-resistant H. pylori in vitro by two 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 measure the rate of development of resistance, H. pylori was grown with subinhibitory concentrations (0.25 x MIC) of plaunotol or metronidazole, and quantitatively plated on to medium containing 4 x MIC of the compounds. This treatment was repeated once more. No plaunotol-resistant colonies 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 membrane might make it difficult for this organism to develop resistance to plaunotol. It was confirmed that the bactericidal effects of plaunotol were also shown against Staphylococcus aureus, Streptococcus pneumoniae, Neisseria gonorrhoeae, Moraxella catarrhalis and Haemophilus influenzae. No such effect was seen against Escherichia coli and Pseudomonas aeruginosa.
Koga
T
T
Biological Research Laboratories, Sankyo Co., Ltd, Tokyo, Japan.
Watanabe
H
H
Kawada
H
H
Takahashi
K
K
Utsui
Y
Y
Domon
H
H
Ishii
C
C
Narita
T
T
Yasuda
H
H
D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D000897:Anti-Ulcer Agents / Q000378:metabolism / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004224:Diterpenes; D004352:Drug Resistance, Microbial; D005233:Fatty Alcohols / Q000378:metabolism / Q000494:pharmacology*; D016480:Helicobacter pylori / Q000187:drug effects* / Q000502:physiology; D008560:Membrane Fluidity / Q000187:drug effects; D008795:Metronidazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests
D000900:Anti-Bacterial Agents; D000897:Anti-Ulcer Agents; D004224:Diterpenes; D005233:Fatty Alcohols; D008795:Metronidazole; C047686:plaunotol