Membrane depolarization prevents cell invasion by Bordetella pertussis adenylate cyclase toxin

A S Otero1, X B Yi, M C Gray

  • 1Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.

Insights

Adenylate cyclase toxin from Bordetella pertussis enters cardiac cells by utilizing the cell membrane's electrical potential. This voltage-dependent process facilitates toxin translocation across the membrane, impacting cellular function.

Area of Science:

  • Microbiology
  • Cell Biology
  • Biochemistry

Background:

  • Adenylate cyclase toxin (ACT) from Bordetella pertussis is a potent calmodulin-activated enzyme.
  • ACT enters eukaryotic cells and disrupts cellular signaling by converting ATP to cAMP.
  • The precise mechanism of ACT cell entry remains largely uncharacterized.

Purpose of the Study:

  • To elucidate the mechanism by which adenylate cyclase toxin enters cardiac myocytes.
  • To investigate the role of the plasma membrane's electrical potential in ACT intoxication.

Main Methods:

  • Cardiac myocytes were utilized to study toxin entry.
  • Electrophysiological techniques were employed to assess voltage dependence.
  • Toxin binding and translocation were analyzed in relation to membrane potential.

Main Results:

  • Adenylate cyclase toxin intoxication of cardiac myocytes is driven and controlled by the plasma membrane's electrical potential.
  • The voltage dependence of intoxication is similar to that of ion channels in excitable membranes.
  • This voltage-sensitive step occurs after toxin binding and involves catalytic domain translocation.

Conclusions:

  • The electrical potential across the plasma membrane is a critical factor in adenylate cyclase toxin entry into cardiac myocytes.
  • Understanding this voltage-sensitive translocation mechanism is key to comprehending Bordetella pertussis pathogenesis.
  • Further research into toxin-membrane interactions can inform therapeutic strategies.

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