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

Czajkowsky DM, Iwamoto H, Szabo G, Cover TL, Shao Z
Biophys J. 2005 89 (5): 3093-101

PMID: 16100263 · PMCID: PMC1366806 · DOI:10.1529/biophysj.105.066746

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.

MeSH Terms (17)

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

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