title: Red Blood Cell Susceptibility to Pneumolysin: CORRELATION WITH MEMBRANE BIOCHEMICAL AND PHYSICAL PROPERTIES.
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.
authors.affiliation: From the College of Life and Environmental Sciences, School of Biosciences, University of Exeter, Exeter EX4 4QD, United Kingdom, m.bokori-brown@exeter.ac.uk.
authors.forename: Monika
authors.initials: M
authors.lastname: Bokori-Brown
authors.affiliation: the College of Engineering, Mathematics and Physical Sciences, School of Physics, University of Exeter, Exeter EX4 4QL, United Kingdom.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Petrov
authors.affiliation: the College of Engineering, Mathematics and Physical Sciences, School of Physics, University of Exeter, Exeter EX4 4QL, United Kingdom.
authors.forename: Mawya A
authors.initials: MA
authors.lastname: Khafaji
authors.affiliation: the Institute of Microbiology and Infection, University of Birmingham, Birmingham B15 2TT, United Kingdom.
authors.forename: Muhammad K
authors.initials: MK
authors.lastname: Mughal
authors.affiliation: the Department of Biological Sciences, Birkbeck College, Malet Street, London WC1E 7HX, United Kingdom.
authors.forename: Claire E
authors.initials: CE
authors.lastname: Naylor
authors.affiliation: the Department of Diabetes and Vascular Medicine, University of Exeter Medical School, Barrack Road, Exeter EX2 5AX, United Kingdom, the National Institute for Health Research Exeter Clinical Research Facility, Royal Devon and Exeter National Health Service Foundation Trust, Exeter EX2 5DW, United Kingdom, and.
authors.forename: Angela C
authors.initials: AC
authors.lastname: Shore
authors.affiliation: the Department of Diabetes and Vascular Medicine, University of Exeter Medical School, Barrack Road, Exeter EX2 5AX, United Kingdom, the National Institute for Health Research Exeter Clinical Research Facility, Royal Devon and Exeter National Health Service Foundation Trust, Exeter EX2 5DW, United Kingdom, and.
authors.forename: Kim M
authors.initials: KM
authors.lastname: Gooding
authors.affiliation: the Department of Diabetes and Vascular Medicine, University of Exeter Medical School, Barrack Road, Exeter EX2 5AX, United Kingdom, the National Institute for Health Research Exeter Clinical Research Facility, Royal Devon and Exeter National Health Service Foundation Trust, Exeter EX2 5DW, United Kingdom, and.
authors.forename: Francesco
authors.initials: F
authors.lastname: Casanova
authors.affiliation: the Institute of Microbiology and Infection, University of Birmingham, Birmingham B15 2TT, United Kingdom.
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Mitchell
authors.affiliation: From the College of Life and Environmental Sciences, School of Biosciences, University of Exeter, Exeter EX4 4QD, United Kingdom.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Titball
authors.affiliation: the College of Engineering, Mathematics and Physical Sciences, School of Physics, University of Exeter, Exeter EX4 4QL, United Kingdom.
authors.forename: C Peter
authors.initials: CP
authors.lastname: Winlove
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000494:pharmacology; D001427:Bacterial Toxins / Q000737:chemistry / Q000494:pharmacology; D003920:Diabetes Mellitus / Q000378:metabolism*; D004910:Erythrocyte Membrane / Q000378:metabolism; D005260:Female; D006460:Hemolysin Proteins / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D013296:Streptococcus pneumoniae / Q000737:chemistry*; D013301:Streptolysins / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae; C020452:Clostridium perfringens theta-toxin
keywords: aging; bacterial toxin; bending rigidity; diabetes; dipole potential; erythrocyte; membrane biophysics; oxidative stress; pneumolysin; surface potential