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Invasion of Human Cells by a Bacterial Pathogen
Published on: March 21, 2011
Membrane depolarization prevents cell invasion by Bordetella pertussis adenylate cyclase toxin
1Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
Abstract:
Adenylate cyclase toxin from Bordetella pertussis is a 177-kDa calmodulin-activated enzyme that has the ability to enter eukaryotic cells and convert endogenous ATP into cAMP. Little is known, however, about the mechanism of cell entry. We now demonstrate that intoxication of cardiac myocytes by adenylate cyclase toxin is driven and controlled by the electrical potential across the plasma membrane. The steepness of the voltage dependence of intoxication is comparable with that previously observed for the activation of K+ and Na+ channels of excitable membranes. The voltage-sensitive process is downstream from toxin binding to the cell surface and appears to correspond to the translocation of the catalytic domain across the membrane.
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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