{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T16:59:15Z","timestamp":1778605155376,"version":"3.51.4"},"reference-count":56,"publisher":"Georg Thieme Verlag KG","issue":"03","funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["DFG HA 3125\/8-1 project no. 523973396 to Sv.H."],"award-info":[{"award-number":["DFG HA 3125\/8-1 project no. 523973396 to Sv.H."]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:p>\n            Background\u2003Platelets prevent extravasation of capillary fluids into the pulmonary interstitial tissue by sealing gaps in inflamed endothelium. This reduces respiratory distress associated with pneumonia. Streptococcus pneumoniae is the leading cause of severe community-acquired pneumonia. Pneumococci produce pneumolysin (PLY), which forms pores in membranes of eukaryotic cells including platelets. Additionally, pneumococci express neuraminidases, which cleave sialic acid residues from eukaryotic glycoproteins. In this study, we investigated the effect of desialylation on PLY binding and pore formation on platelets.<\/jats:p><jats:p>\n            Materials and Methods\u2003We incubated human platelets with purified neuraminidases and PLY, or nonencapsulated S. pneumoniae D39\/TIGR4 and isogenic mutants deficient in PLY and\/or NanA. We assessed platelet desialylation, PLY binding, and pore formation by flow cytometry. We also analyzed the inhibitory potential of therapeutic immunoglobulin G preparations (IVIG [intravenous immunoglobulin]).<\/jats:p><jats:p>\n            Results\u2003Wild-type pneumococci cause desialylation of platelet glycoproteins by neuraminidases, which is reduced by 90 to 100% in NanA-deficient mutants. NanC, cleaving only \u03b12,3-linked sialic acid, induced platelet desialylation. PLY binding to platelets then x2doubled (p\u2009=\u20090.0166) and pore formation tripled (p\u2009=\u20090.0373). A neuraminidase cleaving \u03b12,3-, \u03b12,6-, and \u03b12,8-linked sialic acid like NanA was even more efficient. Addition of polyvalent IVIG (5\u2009mg\/mL) decreased platelet desialylation induced by NanC up to 90% (p\u2009=\u20090.263) and reduced pore formation &gt;95% (p\u2009&lt;\u20090.0001) when incubated with pneumococci.<\/jats:p><jats:p>\n            Conclusion\u2003Neuraminidases are key virulence factors of pneumococci and desialylate platelet glycoproteins, thereby unmasking PLY-binding sites. This enhances binding of PLY and pore formation showing that pneumococcal neuraminidases and PLY act in concert to kill platelets. However, human polyvalent immunoglobulin G preparations are promising agents for therapeutic intervention during severe pneumococcal pneumonia.<\/jats:p>","DOI":"10.1055\/a-2369-8680","type":"journal-article","created":{"date-parts":[[2024,7,20]],"date-time":"2024-07-20T00:00:35Z","timestamp":1721433635000},"page":"243-254","source":"Crossref","is-referenced-by-count":4,"title":["Pneumococcal Neuraminidases Increase Platelet Killing by Pneumolysin"],"prefix":"10.1055","volume":"125","author":[{"given":"Kristin J.","family":"Fritsch","sequence":"additional","affiliation":[{"name":"Department of Transfusion Medicine, Institute of Transfusion Medicine, University Medicine Greifswald, Greifswald, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Kr\u00fcger","sequence":"additional","affiliation":[{"name":"Department of Transfusion Medicine, Institute of Transfusion Medicine, University Medicine Greifswald, Greifswald, Germany"},{"name":"Department of Molecular Genetics and Infection Biology, Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Handtke","sequence":"additional","affiliation":[{"name":"Department of Transfusion Medicine, Institute of Transfusion Medicine, University Medicine Greifswald, Greifswald, Germany"},{"name":"Department of Transfusion Medicine, Institute of Transfusion Medicine, University Medicine Rostock, Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas P.","family":"Kohler","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Infection Biology, Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arina","family":"Ozhiganova","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Infection Biology, Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristin","family":"Jahn","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Infection Biology, Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Wesche","sequence":"additional","affiliation":[{"name":"Department of Transfusion Medicine, Institute of Transfusion Medicine, University Medicine Greifswald, Greifswald, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8343-7336","authenticated-orcid":false,"given":"Andreas","family":"Greinacher","sequence":"additional","affiliation":[{"name":"Department of Transfusion Medicine, Institute of Transfusion Medicine, University Medicine Greifswald, Greifswald, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6382-6681","authenticated-orcid":false,"given":"Sven","family":"Hammerschmidt","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Infection Biology, Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2024,8,20]]},"reference":[{"issue":"11","key":"ref1","doi-asserted-by":"crossref","first-page":"2844","DOI":"10.1182\/blood.V81.11.2844.2844","article-title":"Differentiation and proliferation of hematopoietic stem cells","volume":"81","author":"M Ogawa","year":"1993","journal-title":"Blood"},{"issue":"02","key":"ref2","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1111\/bjh.14653","article-title":"Platelets: much more than bricks 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