Red Blood Cell Susceptibility to Pneumolysin: CORRELATION WITH MEMBRANE BIOCHEMICAL AND PHYSICAL PROPERTIES

Monika Bokori-Brown, Peter G Petrov, Mawya A Khafaji, Muhammad K Mughal, Claire E Naylor, Angela C Shore, Kim M Gooding, Francesco Casanova, Tim J Mitchell, Richard W Titball, C Peter Winlove

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)
164 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)10210-27
Number of pages18
JournalJournal of Biological Chemistry
Volume291
Issue number19
Early online date16 Mar 2016
DOIs
Publication statusPublished - 6 May 2016

Keywords

  • bacterial toxin
  • membrane biophysics
  • erythrocyte
  • oxidative stress
  • aging
  • diabetes
  • pneumolysin
  • bending rigidity
  • surface potential
  • dipole potential

Fingerprint

Dive into the research topics of 'Red Blood Cell Susceptibility to Pneumolysin: CORRELATION WITH MEMBRANE BIOCHEMICAL AND PHYSICAL PROPERTIES'. Together they form a unique fingerprint.

Cite this