{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T05:55:46Z","timestamp":1771998946183,"version":"3.50.1"},"reference-count":29,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T00:00:00Z","timestamp":1660003200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82060766"],"award-info":[{"award-number":["82060766"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81861138046"],"award-info":[{"award-number":["81861138046"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Pneumolysin (PLY) is a significant virulence factor of Streptococcus pneumoniae (S. pneumoniae), able to break through the defense system of a host and mediate the occurrence of a series of infections. Therefore, PLY as the most ideal target to prevent S. pneumoniae infection has received more and more attention and research. Corilagin is a tannic acid that exhibits excellent inhibition of PLY oligomers without bacteriostatic activity to S. pneumoniae. Herein, hemolytic activity assays, cell viability tests and western blot experiments are executed to evaluate the antivirulence efficacy of corilagin against PLY in vitro. Colony observation, hematoxylin and eosin (H&amp;E) staining and cytokines of bronchoalveolar lavage fluid (BALF) are applied to assess the therapeutic effect of corilagin in mice infected by S. pneumoniae. The results indicate the related genes of corilagin act mainly via enrichment in pathways associated with pneumonia disease. Furthermore, molecular docking and molecular dynamics simulations show that corilagin might bind with domains 3 and 4 of PLY and interfere with its hemolytic activity, which is further confirmed by the site-directed mutagenesis of PLY. Additionally, corilagin limits PLY oligomer production without impacting PLY expression in S. pneumoniae cultures. Moreover, corilagin effectively relieves PLY-mediated cell injury without any cytotoxicity, even then reducing the colony count in the lung and the levels of pro-inflammatory factors in BALF and remarkably improving lung lesions. All the results demonstrate that corilagin may be a novel strategy to cope with S. pneumoniae infection by inhibiting PLY oligomerization.<\/jats:p>","DOI":"10.3390\/molecules27165063","type":"journal-article","created":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T04:20:32Z","timestamp":1660105232000},"page":"5063","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Corilagin: A Novel Antivirulence Strategy to Alleviate Streptococcus pneumoniae Infection by Diminishing Pneumolysin Oligomers"],"prefix":"10.3390","volume":"27","author":[{"given":"Qiushuang","family":"Sheng","sequence":"first","affiliation":[{"name":"State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoning","family":"Hou","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nan","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minda","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haoyu","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuming","family":"Deng","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoying","family":"Liang","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China"},{"name":"Department of Internal Medicine, University of South Florida, Tampa, FL 33620, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gefu","family":"Chi","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010010, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3027","DOI":"10.1016\/S0140-6736(16)31593-8","article-title":"Global, regional, and national causes of under-5 mortality in 2000-15: An updated systematic analysis with implications for the Sustainable Development Goals","volume":"388","author":"Liu","year":"2016","journal-title":"Lancet"},{"key":"ref_2","first-page":"100430","article-title":"National, regional, and provincial disease burden attributed to Streptococcus pneumoniae and Haemophilus influenzae type b in children in China: Modelled estimates for 2010\u201317","volume":"22","author":"Lai","year":"2022","journal-title":"Lancet Reg. Health West. Pac."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.3389\/fmicb.2020.01543","article-title":"Pneumolysin: Pathogenesis and Therapeutic Target","volume":"11","author":"Nishimoto","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"497","DOI":"10.2174\/156652408785747924","article-title":"Pneumolysin: A double-edged sword during the host-pathogen interaction","volume":"8","author":"Marriott","year":"2008","journal-title":"Curr. Mol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"140044","DOI":"10.1098\/rsob.140044","article-title":"Incomplete pneumolysin oligomers form membrane pores","volume":"4","author":"Sonnen","year":"2014","journal-title":"Open Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/s00249-015-1106-x","article-title":"Measuring kinetic drivers of pneumolysin pore structure","volume":"45","author":"Gilbert","year":"2016","journal-title":"Eur. Biophys. J. Biophys."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.cell.2005.02.033","article-title":"Structural basis of pore formation by the bacterial toxin pneumolysin","volume":"121","author":"Tilley","year":"2005","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Reboul, C.F., Whisstock, J.C., and Dunstone, M.A. (2014). A New Model for Pore Formation by Cholesterol-Dependent Cytolysins. PLoS Comput. Biol., 10.","DOI":"10.1371\/journal.pcbi.1003791"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1055\/s-2005-925523","article-title":"Streptococcus pneumoniae: Epidemiology, risk factors, and clinical features","volume":"26","author":"Ortqvist","year":"2005","journal-title":"Semin. Respir. Crit. Care Med."},{"key":"ref_10","first-page":"3S","article-title":"Streptococcus pneumoniae: Epidemiology and patterns of resistance","volume":"117","author":"Jacobs","year":"2004","journal-title":"Am. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Harvey, R.M., Hughes, C.E., Paton, A.W., Trappetti, C., Tweten, R.K., and Paton, J.C. (2014). The impact of pneumolysin on the macrophage response to Streptococcus pneumoniae is strain-dependent. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0103625"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.foodchem.2017.04.048","article-title":"Nutraceutical potential of selected wild edible fruits of the Indian Himalayan region","volume":"233","author":"Bhatt","year":"2017","journal-title":"Food Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1111\/1750-3841.14655","article-title":"Composition, Antivirulence Activity, and Active Property Distribution of the Fruit of Terminalia chebula Retz","volume":"84","author":"Li","year":"2019","journal-title":"J. Food Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1248\/bpb.24.1145","article-title":"New TNF-alpha releasing inhibitors, geraniin and corilagin, in leaves of Acer nikoense, Megusurino-ki","volume":"24","author":"Okabe","year":"2001","journal-title":"Biol. Pharm. Bull."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1142\/S0192415X04001849","article-title":"Aqueous extract of Phyllanthus urinaria induces apoptosis in human cancer cells","volume":"32","author":"Huang","year":"2004","journal-title":"Am. J. Chin. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"807509","DOI":"10.3389\/fimmu.2021.807509","article-title":"Corilagin Ameliorates Con A-Induced Hepatic Injury by Restricting M1 Macrophage Polarization","volume":"12","author":"Yan","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_17","first-page":"1656","article-title":"Corilagin potential in inhibiting oxidative and inflammatory stress in LPS-induced murine macrophage cell lines (RAW 264.7)","volume":"24","author":"Widowati","year":"2021","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Haddad, M., Gaudreault, R., Sasseville, G., Nguyen, P.T., Wiebe, H., Van De Ven, T., Bourgault, S., Mousseau, N., and Ramassamy, C. (2022). Molecular Interactions of Tannic Acid with Proteins Associated with SARS-CoV-2 Infectivity. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23052643"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"44161","DOI":"10.18632\/oncotarget.6592","article-title":"Streptococcus pneumoniae induces pyroptosis through the regulation of autophagy in murine microglia","volume":"6","author":"Kim","year":"2015","journal-title":"Oncotarget"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4890","DOI":"10.4049\/jimmunol.1100381","article-title":"Critical roles of ASC inflammasomes in caspase-1 activation and host innate resistance to Streptococcus pneumoniae infection","volume":"187","author":"Fang","year":"2011","journal-title":"J. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.4049\/jimmunol.1401624","article-title":"Neutrophil IL-1beta processing induced by pneumolysin is mediated by the NLRP3\/ASC inflammasome and caspase-1 activation and is dependent on K+ efflux","volume":"194","author":"Karmakar","year":"2015","journal-title":"J. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6199","DOI":"10.1128\/IAI.73.10.6199-6209.2005","article-title":"Cholesterol-dependent cytolysins, a family of versatile pore-forming toxins","volume":"73","author":"Tweten","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1007\/s00408-016-9900-5","article-title":"Pneumolysin Mediates Platelet Activation In Vitro","volume":"194","author":"Nel","year":"2016","journal-title":"Lung"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1126\/science.1176667","article-title":"Antibiotics for emerging pathogens","volume":"325","author":"Fischbach","year":"2009","journal-title":"Science"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1962","DOI":"10.1016\/S0140-6736(10)62225-8","article-title":"Serotype replacement in disease after pneumococcal vaccination","volume":"378","author":"Weinberger","year":"2011","journal-title":"Lancet"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1124\/mol.115.100610","article-title":"Verbascoside Alleviates Pneumococcal Pneumonia by Reducing Pneumolysin Oligomers","volume":"89","author":"Zhao","year":"2016","journal-title":"Mol. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5585","DOI":"10.1016\/j.ejmech.2010.09.008","article-title":"Investigating the structural basis of arylamides to improve potency against M. tuberculosis strain through molecular dynamics simulations","volume":"45","author":"Punkvang","year":"2010","journal-title":"Eur. J. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1111\/jphp.13279","article-title":"Acacetin inhibits Streptococcus pneumoniae virulence by targeting pneumolysin","volume":"72","author":"Li","year":"2020","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2586","DOI":"10.1111\/jcmm.13179","article-title":"Epigallocatechin gallate inhibits Streptococcus pneumoniae virulence by simultaneously targeting pneumolysin and sortase A","volume":"21","author":"Song","year":"2017","journal-title":"J. Cell Mol. Med."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/16\/5063\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:06:11Z","timestamp":1760141171000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/16\/5063"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,9]]},"references-count":29,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["molecules27165063"],"URL":"https:\/\/doi.org\/10.3390\/molecules27165063","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,9]]}}}