A novel in vitro effect of the mucosal protective agent sofalcone--inhibition of chemotactic motility in Helicobacter pylori.
BACKGROUND
Motility of Helicobacter pylori is essential for colonization. H. pylori has been shown to exhibit chemotactic activity toward urea and sodium and bicarbonate ions, which are secreted from the gastric epithelia. The importance of urease activity for chemotactic motility of H. pylori in a viscous environment has also been shown. Consequently, application of drugs inhibiting chemotactic motility has been proposed as a strategy for H. pylori eradication. This inhibitory effect can be evaluated through assay of chemotaxis and swarming.


METHODS
H. pylori CPY3401 and ATCC43504 were grown on brucella agar plates/broth supplemented with 3% horse serum under microaerobic conditions (N2, 85%; O2, 5%; CO2, 10%). For motility assay, H. pylori cells grown on brucella-serum agar were stabbed into motility agar containing 0.35% refined agar in brucella-serum broth and the swarming zone was measured. For the chemotaxis assay, cells were suspended in 10 mM potassium phosphate buffer, pH 7.0, with 3% polyvinyl-pyrrolidone and assayed as described previously. Bacterial swimming in the fluid environment was observed under dark-field microscopy.


RESULTS
Numbers of bacteria attracted toward 1 microM flurofamide were reduced with increasing concentrations of sofalcone (0.2-222 microM). In addition, the size of the swarming zone was reduced in motility agar containing 22 and 222 microM sofalcone. On the other hand, 22 microM sofalcone did not inhibit bacterial growth on day 3. Bacterial swimming speed in brucella broth was slower in the presence of 22 and 222 microM sofalcone than in its absence.


CONCLUSIONS
Sofalcone was found to inhibit chemotactic motility of H. pylori. This drug may be useful for inhibiting the bacterium's ability to colonize the human stomach.
Yoshiyama
H
H
Department of Microbiology, Yamaguchi University School of Medicine, Ube, Japan.
Nakamura
H
H
Okamoto
T
T
Okita
K
K
Nakazawa
T
T
D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology; D047188:Chalcones; D002633:Chemotaxis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D016480:Helicobacter pylori / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D013276:Stomach Ulcer / Q000382:microbiology / Q000517:prevention & control; D014510:Urease / Q000378:metabolism
D000897:Anti-Ulcer Agents; D047188:Chalcones; C035032:sofalcone; D002599:Chalcone; D014510:Urease