Mimicry of a host anion channel by a Helicobacter pylori pore-forming toxin

Biophys J. 2005 Nov;89(5):3093-101. doi: 10.1529/biophysj.105.066746. Epub 2005 Aug 12.

Abstract

Bacterial pore-forming toxins have traditionally been thought to function either by causing an essentially unrestricted flux of ions and molecules across a membrane or by effecting the transmembrane transport of an enzymatically active bacterial peptide. However, the Helicobacter pylori pore-forming toxin, VacA, does not appear to function by either of these mechanisms, even though at least some of its effects in cells are dependent on its pore-forming ability. Here we show that the VacA channel exhibits two of the most characteristic electrophysiological properties of a specific family of cellular channels, the ClC channels: an open probability dependent on the molar ratio of permeable ions and single channel events resolvable as two independent, voltage-dependent transitions. The sharing of such peculiar properties by VacA and host ClC channels, together with their similar magnitudes of conductance, ion selectivities, and localization within eukaryotic cells, suggests a novel mechanism of toxin action in which the VacA pore largely mimics the electrophysiological behavior of a host channel, differing only in the membrane potential at which it closes. As a result, VacA can perturb, but not necessarily abolish, the homeostatic ionic imbalance across a membrane and so change cellular physiology without necessarily jeopardizing vitality.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anions*
  • Bacterial Proteins / chemistry
  • Bacterial Toxins / chemistry
  • Biological Transport
  • Biophysical Phenomena
  • Biophysics
  • Bromides / chemistry
  • Calcium / chemistry
  • Cell Membrane Permeability
  • Electrophysiology
  • Helicobacter pylori / metabolism*
  • Ion Channels
  • Ions
  • Lipid Bilayers
  • Peptides / chemistry
  • Sodium Compounds / chemistry
  • Toxins, Biological / chemistry*

Substances

  • Anions
  • Bacterial Proteins
  • Bacterial Toxins
  • Bromides
  • Ion Channels
  • Ions
  • Lipid Bilayers
  • Peptides
  • Sodium Compounds
  • Toxins, Biological
  • VacA protein, Helicobacter pylori
  • sodium bromide
  • Calcium