{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T04:20:48Z","timestamp":1783398048882,"version":"3.54.6"},"reference-count":40,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2007,9,1]],"date-time":"2007-09-01T00:00:00Z","timestamp":1188604800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2007,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Bacterial toxins such as pneumolysin are key mediators of cytotoxicity in infections. Pneumolysin is a pore-forming toxin released by\n            <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n            , the major cause of bacterial meningitis. We found that pneumolysin is the pneumococcal factor that accounts for the cell death pathways induced by live bacteria in primary neurons. The pore-forming activity of pneumolysin is essential for the induction of mitochondrial damage and apoptosis. Pneumolysin colocalized with mitochondrial membranes, altered the mitochondrial membrane potential, and caused the release of apoptosis-inducing factor and cell death. Pneumolysin induced neuronal apoptosis without activating caspase-1, -3, or -8. Wild-type pneumococci also induced apoptosis without activation of caspase-3, whereas pneumolysin-negative pneumococci activated caspase-3 through the release of bacterial hydrogen peroxide. Pneumolysin caused upregulation of X-chromosome-linked inhibitor of apoptosis protein and inhibited staurosporine-induced caspase activation, suggesting the presence of actively suppressive mechanisms on caspases. In conclusion, our results indicate additional functions of pneumolysin as a mitochondrial toxin and as a determinant of caspase-independent apoptosis. Considering this, blocking of pneumolysin may be a promising cytoprotective strategy in pneumococcal meningitis and other infections.\n          <\/jats:p>","DOI":"10.1128\/iai.00031-07","type":"journal-article","created":{"date-parts":[[2007,6,12]],"date-time":"2007-06-12T02:32:43Z","timestamp":1181615563000},"page":"4245-4254","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":106,"title":["Pneumolysin Causes Neuronal Cell Death through Mitochondrial Damage"],"prefix":"10.1128","volume":"75","author":[{"given":"Johann S.","family":"Braun","sequence":"first","affiliation":[{"name":"Departments of Neurology"},{"name":"Division of Neurology, Department of Internal Medicine, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaf","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Departments of Neurology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Schickhaus","sequence":"additional","affiliation":[{"name":"Departments of Neurology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorette","family":"Freyer","sequence":"additional","affiliation":[{"name":"Departments of Neurology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Dagand","sequence":"additional","affiliation":[{"name":"Departments of Neurology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Bermpohl","sequence":"additional","affiliation":[{"name":"Departments of Neurology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim J.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, University of Glasgow, Glasgow, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingo","family":"Bechmann","sequence":"additional","affiliation":[{"name":"Cell Biology and Neurobiology, Charite\u0301 Universitaetsmedizin Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joerg R.","family":"Weber","sequence":"additional","affiliation":[{"name":"Departments of Neurology"},{"name":"Cell Biology and Neurobiology, Charite\u0301 Universitaetsmedizin Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.2.448-455.1995"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI23223"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0882-4010(86)90027-6"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI12035"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.8.3750-3756.1999"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/6514"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1086\/324013"},{"key":"e_1_3_2_9_2","first-page":"581","volume":"84","year":"1992","unstructured":"Breitschopf, H., G. 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