Glucose and Oxygen Levels Modulate the Pore-Forming Effects of Cholesterol-Dependent Cytolysin Pneumolysin from Streptococcus pneumoniae
- PMID: 38922127
- PMCID: PMC11209487
- DOI: 10.3390/toxins16060232
Glucose and Oxygen Levels Modulate the Pore-Forming Effects of Cholesterol-Dependent Cytolysin Pneumolysin from Streptococcus pneumoniae
Abstract
A major Streptococcus pneumoniae pathogenic factor is the cholesterol-dependent cytolysin pneumolysin, binding membrane cholesterol and producing permanent lytic or transient pores. During brain infections, vascular damage with variable ischemia occurs. The role of ischemia on pneumolysin's pore-forming capacity remains unknown. In acute brain slice cultures and primary cultured glia, we studied acute toxin lysis (via propidium iodide staining and LDH release) and transient pore formation (by analyzing increases in the intracellular calcium). We analyzed normal peripheral tissue glucose conditions (80 mg%), normal brain glucose levels (20 mg%), and brain hypoglycemic conditions (3 mg%), in combinations either with normoxia (8% oxygen) or hypoxia (2% oxygen). At 80 mg% glucose, hypoxia enhanced cytolysis via pneumolysin. At 20 mg% glucose, hypoxia did not affect cell lysis, but impaired calcium restoration after non-lytic pore formation. Only at 3 mg% glucose, during normoxia, did pneumolysin produce stronger lysis. In hypoglycemic (3 mg% glucose) conditions, pneumolysin caused a milder calcium increase, but restoration was missing. Microglia bound more pneumolysin than astrocytes and demonstrated generally stronger calcium elevation. Thus, our work demonstrated that the toxin pore-forming capacity in cells continuously diminishes when oxygen is reduced, overlapping with a continuously reduced ability of cells to maintain homeostasis of the calcium influx once oxygen and glucose are reduced.
Keywords: Streptococcus pneumoniae; astrocytes; brain; hypoglycemia; hypoxia; ischemia; microglia; pneumolysin; pore formation; transient pores.
Conflict of interest statement
The authors declare no conflicts of interest.
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References
-
- Canvin J.R., Marvin A.P., Sivakumaran M., Paton J.C., Boulnois G.J., Andrew P.W., Mitchell T.J. The Role of Pneumolysin and Autolysin in the Pathology of Pneumonia and Septicemia in Mice Infected with a Type 2 Pneumococcus. J. Infect. Dis. 1995;172:119–123. doi: 10.1093/infdis/172.1.119. - DOI - PubMed
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