{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T11:03:43Z","timestamp":1761217423409,"version":"build-2065373602"},"reference-count":55,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2011,1,7]],"date-time":"2011-01-07T00:00:00Z","timestamp":1294358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Streptococcus pneumoniae is a common pathogen that causes various infections, such as sepsis and meningitis. A major pathogenic factor of S. pneumoniae is the cholesterol-dependent cytolysin, pneumolysin. It produces cell lysis at high concentrations and apoptosis at lower concentrations. We have shown that sublytic amounts of pneumolysin induce small GTPase-dependent actin cytoskeleton reorganization and microtubule stabilization in human neuroblastoma cells that are manifested by cell retraction and changes in cell shape. In this study, we utilized a live imaging approach to analyze the role of pneumolysin\u2019s pore-forming capacity in the actin-dependent cell shape changes in primary astrocytes. After the initial challenge with the wild-type toxin, a permeabilized cell population was rapidly established within 20\u201340 minutes. After the initial rapid permeabilization, the size of the permeabilized population remained unchanged and reached a plateau. Thus, we analyzed the non-permeabilized (non-lytic) population, which demonstrated retraction and shape changes that were inhibited by actin depolymerization. Despite the non-lytic nature of pneumolysin treatment, the toxin\u2019s lytic capacity remained critical for the initiation of cell shape changes. The non-lytic pneumolysin mutants W433F-pneumolysin and delta6-pneumolysin, which bind the cell membrane with affinities similar to that of the wild-type toxin, were not able to induce shape changes. The initiation of cell shape changes and cell retraction by the wild-type toxin were independent of calcium and sodium influx and membrane depolarization, which are known to occur following cellular challenge and suggested to result from the ion channel-like properties of the pneumolysin pores. Excluding the major pore-related phenomena as the initiation mechanism of cell shape changes, the existence of a more complex relationship between the pore-forming capacity of pneumolysin and the actin cytoskeleton reorganization is suggested.<\/jats:p>","DOI":"10.3390\/toxins3010043","type":"journal-article","created":{"date-parts":[[2011,1,7]],"date-time":"2011-01-07T10:54:14Z","timestamp":1294397654000},"page":"43-62","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Changes in Astrocyte Shape Induced by Sublytic Concentrations of the Cholesterol-Dependent Cytolysin Pneumolysin Still Require Pore-Forming Capacity"],"prefix":"10.3390","volume":"3","author":[{"given":"Christina","family":"F\u00f6rtsch","sequence":"first","affiliation":[{"name":"DFG Membrane, Cytoskeleton Interaction Group, Institute of Pharmacology and Toxicology & Rudolf Virchow Center for Experimental Medicine, University of W\u00fcrzburg, Versbacherstr. 9, 97078 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabrina","family":"Hupp","sequence":"additional","affiliation":[{"name":"DFG Membrane, Cytoskeleton Interaction Group, Institute of Pharmacology and Toxicology & Rudolf Virchow Center for Experimental Medicine, University of W\u00fcrzburg, Versbacherstr. 9, 97078 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiangtao","family":"Ma","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, Level 2, Glasgow Biomedical Research Centre, University of Glasgow, 120 University Place, Glasgow, G12 8TA, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy J.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, Level 2, Glasgow Biomedical Research Centre, University of Glasgow, 120 University Place, Glasgow, G12 8TA, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elke","family":"Maier","sequence":"additional","affiliation":[{"name":"Rudolf Virchow Center for Experimental Medicine, University of W\u00fcrzburg, Versbacherstr. 9, 97078 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roland","family":"Benz","sequence":"additional","affiliation":[{"name":"Rudolf Virchow Center for Experimental Medicine, University of W\u00fcrzburg, Versbacherstr. 9, 97078 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asparouh I.","family":"Iliev","sequence":"additional","affiliation":[{"name":"DFG Membrane, Cytoskeleton Interaction Group, Institute of Pharmacology and Toxicology & Rudolf Virchow Center for Experimental Medicine, University of W\u00fcrzburg, Versbacherstr. 9, 97078 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2011,1,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1055\/s-2005-925523","article-title":"Streptococcus pneumoniae: Epidemiology, risk factors, and clinical feature","volume":"26","author":"Ortqvist","year":"2005","journal-title":"Semin. 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