Extracellular calcium reduction strongly increases the lytic capacity of pneumolysin from streptococcus pneumoniae in brain tissue

Research output: Contribution to journalArticlepeer-review

Authors

  • Carolin Wippel
  • Christina Förtsch
  • Sabrina Hupp
  • Elke Maier
  • Roland Benz
  • Jiangtao Ma
  • Asparouh I Iliev

Colleges, School and Institutes

Abstract

BACKGROUND: Streptococcus pneumoniae causes serious diseases such as pneumonia and meningitis. Its major pathogenic factor is the cholesterol-dependent cytolysin pneumolysin, which produces lytic pores at high concentrations. At low concentrations, it has other effects, including induction of apoptosis. Many cellular effects of pneumolysin appear to be calcium dependent.

METHODS: Live imaging of primary mouse astroglia exposed to sublytic amounts of pneumolysin at various concentrations of extracellular calcium was used to measure changes in cellular permeability (as judged by lactate dehydrogenase release and propidium iodide chromatin staining). Individual pore properties were analyzed by conductance across artificial lipid bilayer. Tissue toxicity was studied in continuously oxygenated acute brain slices.

RESULTS: The reduction of extracellular calcium increased the lytic capacity of the toxin due to increased membrane binding. Reduction of calcium did not influence the conductance properties of individual toxin pores. In acute cortical brain slices, the reduction of extracellular calcium from 2 to 1 mM conferred lytic activity to pathophysiologically relevant nonlytic concentrations of pneumolysin.

CONCLUSIONS: Reduction of extracellular calcium strongly enhanced the lytic capacity of pneumolysin due to increased membrane binding. Thus, extracellular calcium concentration should be considered as a factor of primary importance for the course of pneumococcal meningitis.

Details

Original languageEnglish
Pages (from-to)930-6
Number of pages7
JournalThe Journal of Infectious Diseases
Volume204
Issue number6
Publication statusPublished - 15 Sep 2011

Keywords

  • Animals, Animals, Newborn, Astrocytes, Bacterial Proteins, Brain, Calcium, Cell Line, Cell Membrane Permeability, Enzyme Inhibitors, L-Lactate Dehydrogenase, Mice, Mice, Inbred C57BL, Streptococcus pneumoniae, Streptolysins