Synergistic Inhibition of Membrane ATPase and Cell Growth of Helicobacter pylori by ATPase Inhibitors

  • Ki, Mi-Ran (Graduate School of Biotechnology, Korea University) ;
  • Yun, Soon-Kyu (Graduate School of Biotechnology, Korea University) ;
  • Lim, Wang-Jin (Graduate School of Biotechnology, Korea University) ;
  • Hong, Bum-Shik (Graduate School of Biotechnology, Korea University) ;
  • Hwang, Se-Young (Graduate School of Biotechnology, Korea University)
  • 발행 : 1999.08.01

초록

Helicobacter pylori were found to be resistant to azide but sensitive to vanadate, suggesting that defect in the P-type ATPase activity rather than F-type ATPase would be lethal to cell survival or growth. To elucidate the relationship between this enzyme inhibition and H. pylori death, we determined the effect of omeprazole (OMP) plus vanadate on enzyme activity and cell growth. The minimum inhibitory concentration (MIC; ca. 0.8$\mu$mol/disk) of vanadate for H. pylori growth was lowered over l0-fold with the aid of OMP, whereby its inhibitory potential toward the P-type ATPase activity was diametrically increased. Alternatively, we found that this enzyme activity was essential for active transport in H. pylori. From these observations, we strongly suggest that the immediate cause of the growth inhibition of H. pylori cells with OMP and/or vanadate might be defective in the cell's active transport due to the lack of P-type ATPase activity. From the spectral data with circular dichroism (CD) spectroscopy, we found that activated OMP (OAS) at concentration below MIC did not disrupt helical structures of membrane proteins. Separately, we determined the cytopathic effect of OAS by SDS-PAGE, indicating the change in the production of cytoplasmic protein but not cell membrane.

키워드

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