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14:29
Visualization of Bacterial Toxin Induced Responses Using Live Cell Fluorescence Microscopy
Published on: October 1, 2012
Aggregatibacter actinomycetemcomitans leukotoxin cytotoxicity occurs through bilayer destabilization
Angela C Brown1, Kathleen Boesze-Battaglia, Yurong Du
1Department of Pathology, University of Pennsylvania School of Dental Medicine, Philadelphia, PA 19104, USA.
Cellular Microbiology
|February 8, 2012
Summary
Aggregatibacter actinomycetemcomitans produces the RTX toxin LtxA, which damages white blood cells by destabilizing cell membranes. This study reveals LtxA induces membrane transitions to non-bilayer phases, causing cell death.
Area of Science:
- Microbiology
- Biochemistry
- Cell Biology
Background:
- Aggregatibacter actinomycetemcomitans is a Gram-negative bacterium found in the human upper aerodigestive tract.
- The bacterium produces the RTX (Repeats in ToXin) toxin LtxA, which is cytotoxic to human white blood cells.
- The precise mechanism of LtxA's membrane interaction and cell surface damage remains unclear.
Purpose of the Study:
- To elucidate the mechanism by which LtxA damages target cell membranes.
- To investigate the role of lipid composition in LtxA-induced membrane damage.
- To determine the biophysical changes in the cell membrane upon LtxA interaction.
Main Methods:
- Liposome-based assays using fluorescent dye release to assess LtxA-induced membrane damage.
- Differential scanning calorimetry (DSC) to study lipid phase transitions.
- (31)P nuclear magnetic resonance ((31)P NMR) spectroscopy to analyze membrane structural changes.
Main Results:
- Liposomes composed of lipids prone to forming nonlamellar phases were susceptible to LtxA-induced dye release.
- Liposomes resistant to forming non-bilayer structures were not damaged by LtxA.
- DSC indicated LtxA lowers the transition temperature to nonlamellar phases; (31)P NMR revealed a bilayer to inverted hexagonal phase transition via an isotropic intermediate.
Conclusions:
- LtxA cytotoxicity is mediated by destabilizing the target cell membrane.
- The toxin promotes transitions from bilayer to non-bilayer lipid phases.
- LtxA's mechanism involves inducing membrane phase changes, leading to cell lysis.
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