{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T23:43:15Z","timestamp":1770680595586,"version":"3.49.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Pneumococcal meningitis, caused by Streptococcus pneumoniae, is exacerbated by factors released during bacterial lysis, triggering inflammation and damage to host cells. Bacteriolytic antibiotics increase inflammation meaning that there is a high unmet medical need for non-bacteriolytic antimicrobials as alternative therapeutic options. Previously,  an 11-amino acid peptide was discovered in the secretome of Klebsiella pneumoniae, named V11A, and was found to inhibit growth of S. pneumoniae in a bacteriostatic and species-specific manner in vitro.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p>Here it is shown  that peptide V11A reduced the growth of not only S. pneumoniae spiked into human cerebrospinal fluid (hCSF) of non-meningitis donors but also S. pneumoniae present naturally in hCSF of a patient with pneumococcal meningitis (hmCSF). In an infant rat model of pneumococcal meningitis, V11A not only reduced the number of S. pneumoniae bacteria in CSF and blood but also reduced the concentration of cytokines GRO\/KC\/CINC-1 (an interleukin-8 (IL-8)-like cytokine in rats) and IL-10 in CSF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Our results support the potential of therapeutic peptide to reduce the bacterial burden and mitigate the inflammatory response in pneumococcal meningitis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2025.1686525","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T07:32:05Z","timestamp":1770622325000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Synthetic peptide V11A reduces bacterial load and inflammation in pneumococcal meningitis"],"prefix":"10.3389","volume":"15","author":[{"given":"Janine","family":"Lux","sequence":"first","affiliation":[{"name":"Institute for Infectious Diseases, Faculty of Medicine, University of Bern","place":["Bern, Switzerland"]},{"name":"Graduate School for Cellular and Biomedical Sciences, University of Bern","place":["Bern, Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Erhardt","sequence":"additional","affiliation":[{"name":"Institute for Infectious Diseases, Faculty of Medicine, University of Bern","place":["Bern, Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linus","family":"Rechsteiner","sequence":"additional","affiliation":[{"name":"Institute for Infectious Diseases, Faculty of Medicine, University of Bern","place":["Bern, Switzerland"]},{"name":"Graduate School for Cellular and Biomedical Sciences, University of Bern","place":["Bern, Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah","family":"Agnew","sequence":"additional","affiliation":[{"name":"Institute for Infectious Diseases, Faculty of Medicine, University of Bern","place":["Bern, Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Hoepner","sequence":"additional","affiliation":[{"name":"Department of Neurology, Bern University Hospital and University of Bern","place":["Bern, Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger","family":"Koller","sequence":"additional","affiliation":[{"name":"Institute for Infectious Diseases, Faculty of Medicine, University of Bern","place":["Bern, Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denis","family":"Grandgirard","sequence":"additional","affiliation":[{"name":"Institute for Infectious Diseases, Faculty of Medicine, University of Bern","place":["Bern, Switzerland"]},{"name":"Multidisciplinary Center for Infectious Diseases, University of Bern","place":["Bern, Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen L.","family":"Leib","sequence":"additional","affiliation":[{"name":"Institute for Infectious Diseases, Faculty of Medicine, University of Bern","place":["Bern, Switzerland"]},{"name":"Multidisciplinary Center for Infectious Diseases, University of Bern","place":["Bern, Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucy J.","family":"Hathaway","sequence":"additional","affiliation":[{"name":"Institute for Infectious Diseases, Faculty of Medicine, University of Bern","place":["Bern, Switzerland"]},{"name":"Multidisciplinary Center for Infectious Diseases, University of Bern","place":["Bern, Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,9]]},"reference":[{"key":"B22","doi-asserted-by":"publisher","first-page":"4193","DOI":"10.2147\/idr.S264692","article-title":"Bacterial isolates from CSF samples and their antimicrobial resistance patterns among children under five suspected to have meningitis in dilla university referral hospital","volume":"13","author":"Awulachew","year":"2020","journal-title":"Infection Drug Resistance"},{"key":"B15","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1097\/QCO.0000000000000416","article-title":"Novel and preclinical treatment strategies in pneumococcal meningitis","volume":"31","author":"Bewersdorf","year":"2018","journal-title":"Curr. Opin. Infect. Dis."},{"key":"B35","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/S0167-7012(02)00226-9","article-title":"A simple micro-growth assay for enumerating bacteria","volume":"53","author":"Brewster","year":"2003","journal-title":"J. Microbiol. Methods"},{"key":"B3","unstructured":"Clinical Features of Pneumococcal Diseases\n          \n          2022"},{"key":"B19","doi-asserted-by":"publisher","first-page":"e1123","DOI":"10.1212\/nxi.0000000000001123","article-title":"CSF neurofilament light chain concentrations predict outcome in bacterial meningitis","volume":"9","author":"Chekrouni","year":"2022","journal-title":"Neurol. Neuroimmunol Neuroinflamm"},{"key":"B37","doi-asserted-by":"publisher","first-page":"4408","DOI":"10.1128\/JCM.41.9.4408-4410.2003","article-title":"Chemically defined media for growth of haemophilus influenzae strains","volume":"41","author":"Coleman","year":"2003","journal-title":"J. Clin. Microbiol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"3928","DOI":"10.1128\/aac.48.10.3928-3933.2004","article-title":"Daptomycin is highly efficacious against penicillin-resistant and penicillin- and quinolone-resistant pneumococci in experimental meningitis","volume":"48","author":"Cottagnoud","year":"2004","journal-title":"Antimicrobial Agents Chemotherapy"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1084\/jem.174.5.1209","article-title":"Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes","volume":"174","author":"de Waal Malefyt","year":"1991","journal-title":"J. Exp. Med."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2024.106484","article-title":"Spatio-temporal brain invasion pattern of Streptococcus pneumoniae and dynamic changes in the cellular environment in bacteremia-derived meningitis","volume":"195","author":"Farmen","year":"2024","journal-title":"Neurobiol. Dis."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.1106596","article-title":"Streptococcus pneumoniae meningitis and the CNS barriers","volume":"12","author":"Gil","year":"2023","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1086\/654819","article-title":"Proteomic analysis of cerebrospinal fluid in pneumococcal meningitis reveals potential biomarkers associated with survival","volume":"202","author":"Goonetilleke","year":"2010","journal-title":"J. Infect. Dis."},{"key":"B11","doi-asserted-by":"publisher","first-page":"2173","DOI":"10.1128\/aac.01014-06","article-title":"Prevention of brain injury by the nonbacteriolytic antibiotic daptomycin in experimental pneumococcal meningitis","volume":"51","author":"Grandgirard","year":"2007","journal-title":"Antimicrobial Agents Chemotherapy"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.150269","article-title":"Streptococcus pneumoniae capsule determines disease severity in experimental pneumococcal meningitis","volume":"6","author":"Hathaway","year":"2016","journal-title":"Open Biol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"123","DOI":"10.3109\/00016489709118003","article-title":"Production and gene expression of IL-8-like cytokine GRO\/CINC-1 in rat nasal mucosa","volume":"117","author":"Himi","year":"1997","journal-title":"Acta Otolaryngol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1186\/s12974-019-1491-7","article-title":"Pneumolysin and the bacterial capsule of Streptococcus pneumoniae cooperatively inhibit taxis and motility of microglia","volume":"16","author":"Hupp","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"B8","doi-asserted-by":"publisher","first-page":"5032","DOI":"10.1038\/s41467-022-32624-2","article-title":"Pneumolysin boosts the neuroinflammatory response to Streptococcus pneumoniae through enhanced endocytosis","volume":"13","author":"Hupp","year":"2022","journal-title":"Nat. Commun."},{"key":"B5","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1016\/S1473-3099(02)00450-4","article-title":"Pathogenesis and pathophysiology of pneumococcal meningitis","volume":"2","author":"Koedel","year":"2002","journal-title":"Lancet Infect. Dis."},{"key":"B16","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1093\/cid\/ciab477","article-title":"Pneumococcal meningitis in adults: A prospective nationwide cohort study over a 20-year period","volume":"74","author":"Koelman","year":"2022","journal-title":"Clin. Infect. Dis."},{"key":"B32","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1111\/j.1574-695X.1996.tb00084.x","article-title":"Interleukin-10 inhibits neutrophil phagocytic and bactericidal activity","volume":"15","author":"Laichalk","year":"1996","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1186\/s12974-020-01966-3","article-title":"Evaluation of neurofilament light chain in the cerebrospinal fluid and blood as a biomarker for neuronal damage in experimental pneumococcal meningitis","volume":"17","author":"Le","year":"2020","journal-title":"J. Neuroinflamm."},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108524","article-title":"Direct measurement of cerebrospinal fluid production in mice","volume":"33","author":"Liu","year":"2020","journal-title":"Cell Rep."},{"key":"B26","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1186\/s12987-022-00382-4","article-title":"Measurements of cerebrospinal fluid production: a review of the limitations and advantages of current methodologies","volume":"19","author":"Liu","year":"2022","journal-title":"Fluids Barriers CNS"},{"key":"B14","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1080\/02724936.1995.11747749","article-title":"Inflammatory response in bacterial meningitis: cytokine levels in the cerebrospinal fluid","volume":"15","author":"Low","year":"1995","journal-title":"Ann. Trop. Paediatr."},{"key":"B17","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1038\/s42003-024-06113-9","article-title":"Klebsiella pneumoniae peptide hijacks a Streptococcus pneumoniae permease to subvert pneumococcal growth and colonization","volume":"7","author":"Lux","year":"2024","journal-title":"Commun. Biol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1128\/cmr.00008-11","article-title":"Pathogenesis and pathophysiology of pneumococcal meningitis","volume":"24","author":"Mook-Kanamori","year":"2011","journal-title":"Clin. Microbiol. Rev."},{"key":"B31","doi-asserted-by":"publisher","first-page":"19920","DOI":"10.1038\/s41598-021-99190-3","article-title":"Cytokine response in cerebrospinal fluid of meningitis patients and outcome associated with pneumococcal serotype","volume":"11","author":"M\u00fcller","year":"2021","journal-title":"Sci. Rep."},{"key":"B2","doi-asserted-by":"publisher","first-page":"166","DOI":"10.3201\/eid2801.210956","article-title":"Streptococcus pneumoniae serotypes associated with death, South Africa, 2012-2018","volume":"28","author":"M\u00fcller","year":"2022","journal-title":"Emerging Infect. Dis."},{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines13050498","article-title":"The new era of pneumococcal vaccination in adults: what is next","volume":"13","author":"Ozisik","year":"2025","journal-title":"Vaccines"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.lana.2025.101120","article-title":"The epidemiology of bacterial meningitis in the United States during 2008\u20132023: an analysis of active, laboratory, population-based, multistate surveillance data","volume":"47","author":"Prasad","year":"2025","journal-title":"Lancet"},{"key":"B36","doi-asserted-by":"publisher","first-page":"000904","DOI":"10.1099\/mgen.0.000904","article-title":"PneumoKITy: A fast, flexible, specific, and sensitive tool for Streptococcus pneumoniae serotype screening and mixed serotype detection from genome sequence data","volume":"8","author":"Sheppard","year":"2022","journal-title":"Microb. Genom"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1956","DOI":"10.4049\/jimmunol.158.4.1956","article-title":"C-X-C and C-C chemokines are expressed in the cerebrospinal fluid in bacterial meningitis and mediate chemotactic activity on peripheral blood-derived polymorphonuclear and mononuclear cells","volume":"158","author":"Spanaus","year":"1997","journal-title":"vitro. J. Immunol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"555","DOI":"10.2170\/jjphysiol.51.555","article-title":"Effects of pCO(2) on the CSF turnover rate in T(1)-weighted magnetic resonance imaging","volume":"51","author":"Takamata","year":"2001","journal-title":"Japanese J. Physiol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1093\/infdis\/151.3.528","article-title":"Effects of ampicillin and corticosteroids on brain water content, cerebrospinal fluid pressure, and cerebrospinal fluid lactate levels in experimental pneumococcal meningitis","volume":"151","author":"Tauber","year":"1985","journal-title":"J. Infect. Dis."},{"key":"B34","doi-asserted-by":"publisher","first-page":"2465","DOI":"10.1002\/eji.1830250909","article-title":"Differential effects of interleukin-10 on the expression of HLA class II and CD1 molecules induced by granulocyte\/macrophage colony-stimulating factor\/interleukin-4","volume":"25","author":"Thomssen","year":"1995","journal-title":"Eur. J. Immunol."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fnhum.2021.737217","article-title":"A brief overview of the cerebrospinal fluid system and its implications for brain and spinal cord diseases","volume":"15","author":"Wichmann","year":"2022","journal-title":"Front. Hum. Neurosci."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1686525\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T07:32:08Z","timestamp":1770622328000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1686525\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,9]]},"references-count":35,"alternative-id":["10.3389\/fcimb.2025.1686525"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2025.1686525","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,9]]},"article-number":"1686525"}}