Red Blood Cell Susceptibility to Pneumolysin: Correlation with Membrane Biochemical and Physical Properties.
Journal of Biological Chemistry
American Society for Biochemistry and Molecular Biology
Copyright © 2016, The American Society for Biochemistry and Molecular Biology. This is the author accepted manuscript. The final version is available from American Society for Biochemistry and Molecular Biology via the DOI in this record.
This study investigated the effect of the biochemical and biophysical properties of the plasma membrane as well as membrane morphology on the susceptibility of human red blood cells to the cholesterol-dependent cytolysin pneumolysin, a key virulence factor of Streptococcus pneumoniae, using single cell studies. We show a correlation between the physical properties of the membrane (bending rigidity, surface and dipole electrostatic potentials) and the susceptibility of red blood cells to pneumolysin-induced haemolysis. We demonstrate that biochemical modifications of the membrane induced by oxidative stress, lipid scrambling and artificial cell aging modulate the cell response to the toxin. We provide evidence that the diversity of response to pneumolysin in diabetic red blood cells correlates with levels of glycated haemoglobin (Hba1c) and that the mechanical properties of the red blood cell plasma membrane are altered in diabetes. Finally, we show that diabetic red blood cells are more resistant to pneumolysin and the related toxin perfringolysin O relative to healthy red blood cells. Taken together, these studies indicate that the diversity of cell response to pneumolysin within a population of human red blood cells is influenced by the biophysical and biochemical status of the plasma membrane and the chemical and/or oxidative stress prehistory of the cell.
The work was supported by the National Institute for Health Research (NIHR) Exeter Clinical Research Facility. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. We also thank E. Green, S. A. Jewell, P. Gologan, M. J. Smallwood and R. Tennant for their help with the experimental techniques.
First published online on March 16, 2016