Crossref journal-article
American Society for Microbiology
Infection and Immunity (235)
Abstract

ABSTRACT The Helicobacter pylori vacuolating cytotoxin (VacA) induces the degenerative vacuolation of mammalian cells both in vitro and in vivo. Here, we demonstrate that plasma membrane cholesterol is essential for vacuolation of mammalian cells by VacA. Vacuole biogenesis in multiple cell lines was completely blocked when cholesterol was extracted selectively from the plasma membrane by using β-cyclodextrins. Moreover, increasing plasma membrane cholesterol levels strongly potentiated VacA-induced vacuolation. In contrast, inhibiting de novo biosynthesis of cholesterol with lovastatin or compactin had no detectable effect on vacuolation. While depletion of plasma membrane cholesterol has been shown to interfere with both clathrin-mediated endocytosis and caveola-dependent endocytosis, neither of these two internalization pathways was found to be essential for vacuolation of cells by VacA. Depleting plasma membrane cholesterol attenuated the entry of VacA into HeLa cells. In addition, β-cyclodextrin reagents blocked vacuolation of cells that were either preloaded with VacA or had VacA directly expressed within the cytosol. Collectively, our results suggest that plasma membrane cholesterol is important for both the intoxication mechanism of VacA and subsequent vacuole biogenesis.

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Patel, H. K., Willhite, D. C., Patel, R. M., Ye, D., Williams, C. L., Torres, E. M., Marty, K. B., MacDonald, R. A., & Blanke, S. R. (2002). Plasma Membrane Cholesterol Modulates Cellular Vacuolation Induced by the Helicobacter pylori Vacuolating Cytotoxin. Infection and Immunity, 70(8), 4112–4123.

Authors 9
  1. Hetal K. Patel (first)
  2. David C. Willhite (additional)
  3. Rakhi M. Patel (additional)
  4. Dan Ye (additional)
  5. Christopher L. Williams (additional)
  6. Eric M. Torres (additional)
  7. Kent B. Marty (additional)
  8. Robert A. MacDonald (additional)
  9. Steven R. Blanke (additional)
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Dates
Type When
Created 23 years, 1 month ago (July 28, 2002, 7:07 p.m.)
Deposited 3 years, 5 months ago (March 4, 2022, 10:02 p.m.)
Indexed 1 year ago (Aug. 11, 2024, 3:07 p.m.)
Issued 23 years, 1 month ago (Aug. 1, 2002)
Published 23 years, 1 month ago (Aug. 1, 2002)
Published Print 23 years, 1 month ago (Aug. 1, 2002)
Funders 0

None

@article{Patel_2002, title={Plasma Membrane Cholesterol Modulates Cellular Vacuolation Induced by the Helicobacter pylori Vacuolating Cytotoxin}, volume={70}, ISSN={1098-5522}, url={http://dx.doi.org/10.1128/iai.70.8.4112-4123.2002}, DOI={10.1128/iai.70.8.4112-4123.2002}, number={8}, journal={Infection and Immunity}, publisher={American Society for Microbiology}, author={Patel, Hetal K. and Willhite, David C. and Patel, Rakhi M. and Ye, Dan and Williams, Christopher L. and Torres, Eric M. and Marty, Kent B. and MacDonald, Robert A. and Blanke, Steven R.}, year={2002}, month=aug, pages={4112–4123} }