Abstract
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 and surface and dipole electrostatic potentials) and the susceptibility of red blood cells to pneumolysin-induced hemolysis. 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 hemoglobin 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 pre-history of the cell.
Highlights
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 and the susceptibility of red blood cells to pneumolysin-induced hemolysis
We provide evidence that the diversity of response to pneumolysin in diabetic red blood cells correlates with levels of glycated hemoglobin and that the mechanical properties of the red blood cell plasma membrane are altered in diabetes
Summary
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. Individual RBCs within a population differ significantly (3) with respect to their shape, volume, and surface area Some of these changes are related to cell age, due to the variety of mechanical and chemical stresses that an RBC undergoes in its life span of ϳ120 days (4, 5), and others can be associated with diseases, such as diabetes and with acute conditions, such as sepsis, among many others (6), and are likely to be present in the membranes of many other cell types. Previous work on bulk cell preparations revealed that in addition to its normal discocytic shape, the RBC at rest can assume a variety of other distinct shapes, such as echinocytes and acanthocytes, characterized by exterior projections, and stomatocytes with cup-shaped invaginations (7) Many of these unusual shapes appear in normal blood at a frequency of about 1%. An increase of 13% in echinocytes was observed in patients suffering from chronic hepatitis (13), and in neuroacanthocytosis syndromes, a group of rare neurodegenerative diseases that mainly affect children and young adults, acanthocytes appear with a frequency of 12– 45% (14)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
