{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T10:56:55Z","timestamp":1777892215564,"version":"3.51.4"},"reference-count":53,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T00:00:00Z","timestamp":1716249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Fund","doi-asserted-by":"publisher","award":["160136"],"award-info":[{"award-number":["160136"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Fund","doi-asserted-by":"publisher","award":["20A010"],"award-info":[{"award-number":["20A010"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008273","name":"Novartis Foundation","doi-asserted-by":"publisher","award":["160136"],"award-info":[{"award-number":["160136"]}],"id":[{"id":"10.13039\/100008273","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008273","name":"Novartis Foundation","doi-asserted-by":"publisher","award":["20A010"],"award-info":[{"award-number":["20A010"]}],"id":[{"id":"10.13039\/100008273","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>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\u2019s 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.<\/jats:p>","DOI":"10.3390\/toxins16060232","type":"journal-article","created":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T05:40:47Z","timestamp":1716270047000},"page":"232","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Glucose and Oxygen Levels Modulate the Pore-Forming Effects of Cholesterol-Dependent Cytolysin Pneumolysin from Streptococcus pneumoniae"],"prefix":"10.3390","volume":"16","author":[{"given":"Michelle Salom\u00e9","family":"Hoffet","sequence":"first","affiliation":[{"name":"Institute of Anatomy, University of Bern, Baltzerstrasse 2, 3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7072-3832","authenticated-orcid":false,"given":"Nikola S.","family":"Tomov","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, University of Bern, Baltzerstrasse 2, 3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabrina","family":"Hupp","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, University of Bern, Baltzerstrasse 2, 3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy J.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1343-2967","authenticated-orcid":false,"given":"Asparouh I.","family":"Iliev","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, University of Bern, Baltzerstrasse 2, 3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Gessner, B.D., Mueller, J.E., and Yaro, S. 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