LacR and TrxB are key virulence factors involved in pneumococcal meningitis as identified by a genome-wide association study

LacR and TrxB are key virulence factors involved in pneumococcal meningitis as identified by a genome-wide association study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article LacR and TrxB are key virulence factors involved in pneumococcal meningitis as identified by a genome-wide association study Diederik van de Beek, Rutger Koning, Kin Ki Jim, Philip Kremer, and 12 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6771075/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Pneumococcal meningitis is the most common form of bacterial meningitis, with high case fatality rates. Bacterial genetics influence disease severity and patient outcome, but the mechanisms underlying pneumococcal meningitis pathogenesis remain poorly understood. Here, we evaluated top variants from a genome-wide association study (GWAS) linking Streptococcus pneumoniae genetic variation to disease outcome. Fifteen isogenic S. pneumoniae knockout mutants were tested for virulence in a zebrafish embryo meningitis model; six showed significantly reduced virulence compared to wild-type, but four were excluded following competitive index and growth assays. Deletion of SPV_1044 (lacR), encoding a lactose phosphotransferase system repressor involved in galactose metabolism, led to delayed growth in galactose and human cerebrospinal fluid in vitro. Deletion of SPV_1393 (trxB), encoding thioredoxin reductase, increased susceptibility to hydrogen peroxide. This proof-of-concept study, combining pathogen GWAS with in vivo validation, identifies two pneumococcal virulence genes linked to disease severity. Health sciences/Neurology/Neurological disorders/Meningitis Biological sciences/Microbiology/Bacteria/Bacterial pathogenesis Streptococcus pneumoniae meningitis virulence zebrafish galactose reactive oxygen species Full Text Additional Declarations There is NO Competing Interest. Supplementary Files TableS4.Primers.xlsx Supplementary Table S4 Supplementaryinformation.pdf Supplementary Information Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6771075","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":476069369,"identity":"f6c1cda3-7304-45bd-99cf-d3763169b872","order_by":0,"name":"Diederik van de 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