{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T02:51:19Z","timestamp":1780455079167,"version":"3.54.1"},"reference-count":43,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2017,1,17]],"date-time":"2017-01-17T00:00:00Z","timestamp":1484611200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,3,8]],"date-time":"2017-03-08T00:00:00Z","timestamp":1488931200000},"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":["mBio"],"published-print":{"date-parts":[[2017,3,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            To improve our understanding about the severity of invasive pneumococcal disease (IPD), we investigated the association between the genotype of\n            <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n            and disease outcomes for 349 bacteremic patients. A pneumococcal genome-wide association study (GWAS) demonstrated a strong correlation between 30-day mortality and the presence of the phage-derived gene\n            <jats:italic>pblB<\/jats:italic>\n            , encoding a platelet-binding protein whose effects on platelet activation were previously unknown. Platelets are increasingly recognized as key players of the innate immune system, and in sepsis, excessive platelet activation contributes to microvascular obstruction, tissue hypoperfusion, and finally multiorgan failure, leading to mortality. Our\n            <jats:italic>in vitro<\/jats:italic>\n            studies revealed that\n            <jats:italic>pblB<\/jats:italic>\n            expression was induced by fluoroquinolones but not by the beta-lactam antibiotic penicillin G. Subsequently, we determined\n            <jats:italic>pblB<\/jats:italic>\n            induction and platelet activation by incubating whole blood with the wild type or a\n            <jats:italic>pblB<\/jats:italic>\n            knockout mutant in the presence or absence of antibiotics commonly administered to our patient cohort.\n            <jats:italic>pblB<\/jats:italic>\n            -dependent enhancement of platelet activation, as measured by increased expression of the \u03b1-granule protein P-selectin, the binding of fibrinogen to the activated \u03b1IIb\u03b23 receptor, and the formation of platelet-monocyte complex occurred irrespective of antibiotic exposure. In conclusion, the presence of\n            <jats:italic>pblB<\/jats:italic>\n            on the pneumococcal chromosome potentially leads to increased mortality in patients with an invasive\n            <jats:italic>S.\u00a0pneumoniae<\/jats:italic>\n            infection, which may be explained by enhanced platelet activation. This study highlights the clinical utility of a bacterial GWAS, followed by functional characterization, to identify bacterial factors involved in disease severity.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            The exact mechanisms causing mortality in invasive pneumococcal disease (IPD) patients are not completely understood. We examined 349 patients with IPD and found in a bacterial genome-wide association study (GWAS) that the presence of the phage-derived gene\n            <jats:italic>pblB<\/jats:italic>\n            was associated with mortality in the first 30\u00a0days after hospitalization. Although\n            <jats:italic>pblB<\/jats:italic>\n            has been extensively studied in\n            <jats:italic>Streptococcus mitis<\/jats:italic>\n            , its consequence for the interaction between platelets and\n            <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n            is largely unknown. Platelets are important in immunity and inflammation, and excessive platelet activation contributes to microvascular obstruction and multiorgan failure, leading to mortality. We therefore developed this study to assess whether the expression of\n            <jats:italic>pblB<\/jats:italic>\n            might increase the risk of death for IPD patients through its effect on enhanced platelet activation. This study also shows the value of integrating extensive bacterial genomics and clinical data in predicting and understanding pathogen virulence, which in turn will help to improve prognosis and therapy.\n          <\/jats:p>","DOI":"10.1128\/mbio.01984-16","type":"journal-article","created":{"date-parts":[[2017,1,18]],"date-time":"2017-01-18T01:25:39Z","timestamp":1484702739000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":29,"title":["Phage-Derived Protein Induces Increased Platelet Activation and Is Associated with Mortality in Patients with Invasive Pneumococcal Disease"],"prefix":"10.1128","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6168-4758","authenticated-orcid":false,"given":"Rahajeng N.","family":"Tunjungputri","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands"},{"name":"Center for Tropical and Infectious Diseases (CENTRID), Faculty of Medicine, Diponegoro University, and Dr. Kariadi Hospital, Semarang, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0554-9919","authenticated-orcid":false,"given":"Fredrick M.","family":"Mobegi","sequence":"additional","affiliation":[{"name":"Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelieke J.","family":"Cremers","sequence":"additional","affiliation":[{"name":"Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands"},{"name":"Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christa E.","family":"van der Gaast-de Jongh","sequence":"additional","affiliation":[{"name":"Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerben","family":"Ferwerda","sequence":"additional","affiliation":[{"name":"Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques F.","family":"Meis","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands"},{"name":"Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nel","family":"Roeleveld","sequence":"additional","affiliation":[{"name":"Department for Health Evidence, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands"},{"name":"Department of Pediatrics, Radboudumc Amalia Children\u2019s Hospital, Radboud University Medical Center, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen D.","family":"Bentley","sequence":"additional","affiliation":[{"name":"Wellcome Trust Sanger Institute, Pathogen Genomics Group, Hinxton, Cambridgeshire, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander S.","family":"Pastura","sequence":"additional","affiliation":[{"name":"Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sacha A. 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