title: Mimicry of a host anion channel by a Helicobacter pylori pore-forming toxin.
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.
authors.affiliation: Department of Molecular Physiology and Biological Physics, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Czajkowsky
authors.forename: Hideki
authors.initials: H
authors.lastname: Iwamoto
authors.forename: Gabor
authors.initials: G
authors.lastname: Szabo
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Cover
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Shao
mesh_terms: D000838:Anions; D001426:Bacterial Proteins / Q000737:chemistry; D001427:Bacterial Toxins / Q000737:chemistry; D001692:Biological Transport; D055592:Biophysical Phenomena; D001703:Biophysics; D001965:Bromides / Q000737:chemistry; D002118:Calcium / Q000737:chemistry; D002463:Cell Membrane Permeability; D004594:Electrophysiology; D016480:Helicobacter pylori / Q000378:metabolism*; D007473:Ion Channels; D007477:Ions; D008051:Lipid Bilayers; D010455:Peptides / Q000737:chemistry; D017670:Sodium Compounds / Q000737:chemistry; D014118:Toxins, Biological / Q000737:chemistry*
chemical_list: D000838:Anions; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D001965:Bromides; D007473:Ion Channels; D007477:Ions; D008051:Lipid Bilayers; D010455:Peptides; D017670:Sodium Compounds; D014118:Toxins, Biological; C074689:VacA protein, Helicobacter pylori; C027938:sodium bromide; D002118:Calcium