Journal of Antimicrobial Chemotherapy, Vol 42, 133-140, Copyright © 1998 by The British Society for Antimicrobial Chemotherapy
T Koga, H Watanabe, H Kawada, K Takahashi, Y Utsui, H Domon, C Ishii, T Narita and H Yasuda
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.
ORIGINAL ARTICLES
Interactions of plaunotol with bacterial membranes
Biological Research Laboratories, Sankyo Co., Ltd, Tokyo, Japan.
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