{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T20:35:09Z","timestamp":1782592509639,"version":"3.54.5"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Ton Duc Thang University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Certain probiotic bacteria have been shown to possess an immunomodulatory effect and a protective effect on influenza infections. Using the Staphylococcus epidermidis K1 colonized mice model, we assessed the effect of nasal administration of glycerol or flavin mononucleotide (FMN) on the production of interleukin (IL)-6 mediated by the severe acute respiratory syndrome coronavirus 2 (SARS2-CoV) nucleocapsid protein (NPP).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>FMN, one of the key electron donors for the generation of electricity facilitated by S. epidermidis ATCC 12228, was detected in the glycerol fermentation medium. Compared to the S. epidermidis ATCC 12228, the S. epidermidis K1 isolate showed significant expression of the electron transfer genes, including pyruvate dehydrogenase (pdh), riboflavin kinase (rk), 1,4-dihydroxy-2-naphthoate octaprenyltransferase (menA), and type II NADH quinone oxidoreductase (ndh2). Institute of cancer research (ICR) mice were intranasally administered with S. epidermidis K1 with or without pretreatment with riboflavin kinase inhibitors, then nasally treated with glycerol or FMN before inoculating the NPP. Furthermore, J774A.1 macrophages were exposed to NPP serum and then treated with NPP of SARS2-CoV. The IL-6 levels in the bronchoalveolar lavage fluid (BALF) of mice and macrophages were quantified using a mouse IL-6 enzyme-linked immunosorbent assay kit.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Here, we report that nasal administration of NPP strongly elevates IL-6 levels in both BALF and J774A.1 macrophages. It is worth noting that NPP-neutralizing antibodies can decrease IL-6 levels in macrophages. The nasal administration of glycerol or FMN to S. epidermidis K1-colonized mice results in a reduction of NPP-induced IL-6 production.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jambio\/lxad179","type":"journal-article","created":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T20:56:02Z","timestamp":1691614562000},"source":"Crossref","is-referenced-by-count":1,"title":["Electrogenic\n                    <i>Staphylococcus epidermidis<\/i>\n                    colonizes nasal cavities and alleviates IL-6 progression induced by the SARS2-CoV nucleocapsid protein"],"prefix":"10.1093","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9160-6734","authenticated-orcid":false,"given":"Enkhbat","family":"Zayabaatar","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences and Engineering, National Central University , Taoyuan 320317 , Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4802-5595","authenticated-orcid":false,"given":"Nguyen Mai Trinh","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Engineering, National Central University , Taoyuan 320317 , Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minh Tan","family":"Pham","sequence":"additional","affiliation":[{"name":"Faculty of Applied Sciences, Ton Duc Thang University , Ho Chi Minh City 700000 , Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,8,9]]},"reference":[{"key":"2023082419252872500_bib1","doi-asserted-by":"crossref","first-page":"151ra124","DOI":"10.1126\/scitranslmed.3003783","article-title":"Sinus microbiome diversity depletion and Corynebacterium tuberculostearicum enrichment mediates rhinosinusitis","volume":"4","author":"Abreu","year":"2012","journal-title":"Sci Transl Med"},{"key":"2023082419252872500_bib2","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1164\/rccm.201407-1240OC","article-title":"Early respiratory microbiota composition determines bacterial succession patterns and respiratory health in children","volume":"190","author":"Biesbroek","year":"2014","journal-title":"Am J Respir Crit Care Med"},{"key":"2023082419252872500_bib3","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/mBio.01725-15","article-title":"Corynebacterium accolens releases antipneumococcal free fatty acids from human nostril and skin surface triacylglycerols","volume":"7","author":"Bomar","year":"2016","journal-title":"mBio"},{"key":"2023082419252872500_bib4","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/d41586-018-06180-z","article-title":"The electrifying energy of gut microbes","volume":"562","author":"Cahoon","year":"2018","journal-title":"Nature"},{"key":"2023082419252872500_bib5","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/s41577-020-0308-3","article-title":"COVID-19: immunopathology and its implications for therapy","volume":"20","author":"Cao","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"2023082419252872500_bib6","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1007\/s00281-017-0629-x","article-title":"Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology","volume":"39","author":"Channappanavar","year":"2017","journal-title":"Semin Immunopathol"},{"key":"2023082419252872500_bib7","first-page":"1","article-title":"Nasal commensal Staphylococcus epidermidis counteracts influenza virus","volume":"6","author":"Chen","year":"2016","journal-title":"Sci Rep"},{"key":"2023082419252872500_bib8","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1002\/jmv.25681","article-title":"Emerging coronaviruses: genome structure, replication, and pathogenesis","volume":"92","author":"Chen","year":"2020","journal-title":"J Med Virol"},{"key":"2023082419252872500_bib9","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/jid.2009.243","article-title":"Selective antimicrobial action is provided by phenol-soluble modulins derived from Staphylococcus epidermidis, a normal resident of the skin","volume":"130","author":"Cogen","year":"2010","journal-title":"J Invest Dermatol"},{"key":"2023082419252872500_bib10","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/s41392-021-00796-w","article-title":"The way of SARS-CoV-2 vaccine development: success and challenges","volume":"6","author":"Dong","year":"2021","journal-title":"Sig Transduct Target Ther"},{"key":"2023082419252872500_bib11","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/s41579-018-0088-y","article-title":"Exporting electrons","volume":"16","author":"Du\u00a0Toit","year":"2018","journal-title":"Nat Rev Micro"},{"key":"2023082419252872500_bib12","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1111\/mmi.13447","article-title":"A partial metabolic pathway enables group b streptococcus to overcome quinone deficiency in a host bacterial community","volume":"102","author":"Franza","year":"2016","journal-title":"Mol Microbiol"},{"key":"2023082419252872500_bib13","doi-asserted-by":"crossref","first-page":"677","DOI":"10.3390\/biomedicines11030677","article-title":"Lactobacillus plantarum generate electricity through flavin mononucleotide-mediated extracellular electron transfer to upregulate epithelial type I collagen expression and thereby promote microbial adhesion to intestine","volume":"11","author":"Ganzorig","year":"2023","journal-title":"Biomedicines"},{"key":"2023082419252872500_bib14","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41522-017-0027-0","article-title":"Redox-active conducting polymers modulate Salmonella biofilm formation by controlling availability of electron acceptors","volume":"3","author":"Gomez-Carretero","year":"2017","journal-title":"npj Biofilms Microbiomes"},{"key":"2023082419252872500_bib15","first-page":"103","article-title":"High-performance liquid chromatographic analysis of demethylmenaquinone and menaquinone mixtures from bacteria","volume":"64","author":"Hiraishi","year":"1988","journal-title":"J Appl Bacteriol"},{"key":"2023082419252872500_bib16","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1093\/clinchem\/48.9.1571","article-title":"Riboflavin, flavin mononucleotide, and flavin adenine dinucleotide in human plasma and erythrocytes at baseline and after low-dose riboflavin supplementation","volume":"48","author":"Hustad","year":"2002","journal-title":"Clin Chem"},{"key":"2023082419252872500_bib17","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/nature09074","article-title":"Staphylococcus epidermidis Esp inhibits Staphylococcus aureus biofilm formation and nasal colonization","volume":"465","author":"Iwase","year":"2010","journal-title":"Nature"},{"key":"2023082419252872500_bib18","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1111\/1751-7915.13994","article-title":"Colonization of nasal cavities by Staphylococcus epidermidis mitigates SARS-CoV-2 nucleocapsid phosphoprotein-induced interleukin (IL)-6 in the lung","volume":"15","author":"Kao","year":"2022","journal-title":"Microb Biotechnol"},{"key":"2023082419252872500_bib19","doi-asserted-by":"crossref","first-page":"e0268251","DOI":"10.1371\/journal.pone.0268251","article-title":"Immunological investigation of a multiepitope peptide vaccine candidate based on main proteins of SARS-CoV-2 pathogen","volume":"17","author":"Khairkhah","year":"2022","journal-title":"PLoS One"},{"key":"2023082419252872500_bib20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40168-019-0691-9","article-title":"Nasal commensal Staphylococcus epidermidis enhances interferon-\u03bb-dependent immunity against influenza virus","volume":"7","author":"Kim","year":"2019","journal-title":"Microbiome"},{"key":"2023082419252872500_bib21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12915-019-0703-z","article-title":"The microbiome of the upper respiratory tract in health and disease","volume":"17","author":"Kumpitsch","year":"2019","journal-title":"BMC Biol"},{"key":"2023082419252872500_bib22","doi-asserted-by":"crossref","first-page":"e0144323","DOI":"10.1371\/journal.pone.0144323","article-title":"Correction: effects of the Staphylococcus aureus and Staphylococcus epidermidis secretomes isolated from the skin microbiota of atopic children on CD4+ T cell activation","volume":"10","author":"Laborel-Preneron","year":"2015","journal-title":"PLoS One"},{"key":"2023082419252872500_bib23","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1038\/nm.2062","article-title":"Commensal bacteria regulate Toll-like receptor 3\u2013dependent inflammation after skin injury","volume":"15","author":"Lai","year":"2009","journal-title":"Nat Med"},{"key":"2023082419252872500_bib24","doi-asserted-by":"crossref","first-page":"187","DOI":"10.4161\/rna.6.2.7727","article-title":"Roseoflavin is a natural antibacterial compound that binds to FMN riboswitches and regulates gene expression","volume":"6","author":"Lee","year":"2009","journal-title":"RNA Biology"},{"key":"2023082419252872500_bib25","doi-asserted-by":"crossref","first-page":"11093","DOI":"10.5897\/AJB11.873","article-title":"Biotechnological synthesis of 1, 3-propanediol using Clostridium ssp","volume":"10","author":"Leja","year":"2011","journal-title":"Afr J Biotechnol"},{"key":"2023082419252872500_bib26","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.jes.2019.07.016","article-title":"Identification of potential electrotrophic microbial community in paddy soils by enrichment of microbial electrolysis cell biocathodes","volume":"87","author":"Li","year":"2020","journal-title":"J Environ Sci"},{"key":"2023082419252872500_bib27","doi-asserted-by":"crossref","first-page":"26892","DOI":"10.1073\/pnas.1915678116","article-title":"Extracellular electron transfer powers flavinylated extracellular reductases in gram-positive bacteria","volume":"116","author":"Light","year":"2019","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023082419252872500_bib28","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1038\/s41586-018-0498-z","article-title":"A flavin-based extracellular electron transfer mechanism in diverse Gram-positive bacteria","volume":"562","author":"Light","year":"2018","journal-title":"Nature"},{"key":"2023082419252872500_bib29","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1038\/s41467-020-20768-y","article-title":"The SARS-CoV-2 nucleocapsid phosphoprotein forms mutually exclusive condensates with RNA and the membrane-associated M protein","volume":"12","author":"Lu","year":"2021","journal-title":"Nat Commun"},{"key":"2023082419252872500_bib30","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/nrmicro.2017.14","article-title":"The microbiota of the respiratory tract: gatekeeper to respiratory health","volume":"15","author":"Man","year":"2017","journal-title":"Nat Rev Micro"},{"key":"2023082419252872500_bib31","doi-asserted-by":"crossref","first-page":"12001","DOI":"10.1038\/s41598-021-91398-7","article-title":"Electricity-producing Staphylococcus epidermidis counteracts Cutibacterium acnes","volume":"11","author":"Marito","year":"2021","journal-title":"Sci Rep"},{"key":"2023082419252872500_bib32","doi-asserted-by":"crossref","first-page":"3968","DOI":"10.1073\/pnas.0710525105","article-title":"Shewanella secretes flavins that mediate extracellular electron transfer","volume":"105","author":"Marsili","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023082419252872500_bib33","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/nature14052","article-title":"Commensal\u2013dendritic-cell interaction specifies a unique protective skin immune signature","volume":"520","author":"Naik","year":"2015","journal-title":"Nature"},{"key":"2023082419252872500_bib34","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1021\/jacs.9b10254","article-title":"Unprecedented properties of phenothiazines unraveled by a NDH-2 bioelectrochemical assay platform","volume":"142","author":"Nakatani","year":"2020","journal-title":"J Am Chem Soc"},{"key":"2023082419252872500_bib35","doi-asserted-by":"crossref","first-page":"eaah4680","DOI":"10.1126\/scitranslmed.aah4680","article-title":"Antimicrobials from human skin commensal bacteria protect against Staphylococcus aureus and are deficient in atopic dermatitis","volume":"9","author":"Nakatsuji","year":"2017","journal-title":"Sci Transl Med"},{"key":"2023082419252872500_bib36","doi-asserted-by":"crossref","DOI":"10.1155\/2020\/8045646","article-title":"The human microbiome and its impacts on health","volume":"2020","author":"Ogunrinola","year":"2020","journal-title":"International Journal of Microbiology"},{"key":"2023082419252872500_bib37","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1093\/ajcn\/77.6.1352","article-title":"Riboflavin (vitamin B-2) and health1,2","volume":"77","author":"Powers","year":"2003","journal-title":"Am J Clin Nutr"},{"key":"2023082419252872500_bib38","doi-asserted-by":"crossref","first-page":"e0169955","DOI":"10.1371\/journal.pone.0169955","article-title":"Isolation and characterization of a novel electrogenic bacterium, Dietzia sp. RNV-4","volume":"12","author":"Sacco","year":"2017","journal-title":"PLoS One"},{"key":"2023082419252872500_bib39","doi-asserted-by":"crossref","first-page":"2762","DOI":"10.1016\/j.jmb.2019.05.029","article-title":"The biosynthesis of flavin cofactors in Listeria monocytogenes","volume":"431","author":"Sebasti\u00e1n","year":"2019","journal-title":"J Mol Biol"},{"key":"2023082419252872500_bib40","doi-asserted-by":"crossref","first-page":"7977","DOI":"10.4049\/jimmunol.174.12.7977","article-title":"Severe acute respiratory syndrome and the innate immune responses: modulation of effector cell function without productive infection","volume":"174","author":"Tseng","year":"2005","journal-title":"J Immunol"},{"key":"2023082419252872500_bib41","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1111\/mmi.13723","article-title":"Generation of the membrane potential and its impact on the motility, ATP production and growth in Campylobacter jejuni","volume":"105","author":"van\u00a0der\u00a0Stel","year":"2017","journal-title":"Mol Microbiol"},{"key":"2023082419252872500_bib42","doi-asserted-by":"crossref","first-page":"12658","DOI":"10.1128\/JVI.79.20.12658-12666.2005","article-title":"Varicella-zoster virus activates inflammatory cytokines in human monocytes and macrophages via Toll-like receptor 2","volume":"79","author":"Wang","year":"2005","journal-title":"J Virol"},{"key":"2023082419252872500_bib43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.virusres.2007.02.007","article-title":"Up-regulation of IL-6 and TNF-\u03b1 induced by SARS-coronavirus spike protein in murine macrophages via NF-\u03bab pathway","volume":"128","author":"Wang","year":"2007","journal-title":"Virus Res"},{"key":"2023082419252872500_bib44","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.3390\/ijms17111870","article-title":"A precision microbiome approach using sucrose for selective augmentation of Staphylococcus epidermidis fermentation against Propionibacterium acnes","volume":"17","author":"Wang","year":"2016","journal-title":"Int J Mol Sci"},{"key":"2023082419252872500_bib45","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1007\/s00253-013-5394-8","article-title":"Staphylococcus epidermidis in the human skin microbiome mediates fermentation to inhibit the growth of Propionibacterium acnes: implications of probiotics in acne vulgaris","volume":"98","author":"Wang","year":"2014","journal-title":"Appl Microbiol Biotechnol"},{"key":"2023082419252872500_bib46","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.3390\/ijms23031813","article-title":"The human microbiota and skin cancer","volume":"23","author":"Woo","year":"2022","journal-title":"Int J Mol Sci"},{"key":"2023082419252872500_bib47","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.virol.2007.04.009","article-title":"Nucleocapsid protein of SARS-CoV activates interleukin-6 expression through cellular transcription factor NF-\u03bab","volume":"365","author":"Zhang","year":"2007","journal-title":"Virology"},{"key":"2023082419252872500_bib48","doi-asserted-by":"crossref","first-page":"2160","DOI":"10.1016\/j.procbio.2006.06.012","article-title":"Overexpression of genes of the dha regulon and its effects on cell growth, glycerol fermentation to 1,3-propanediol and plasmid stability in Klebsiella pneumoniae","volume":"41","author":"Zheng","year":"2006","journal-title":"Process Biochem"}],"container-title":["Journal of Applied Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jambio\/advance-article-pdf\/doi\/10.1093\/jambio\/lxad179\/51098972\/lxad179.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jambio\/article-pdf\/134\/8\/lxad179\/51247031\/lxad179.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jambio\/article-pdf\/134\/8\/lxad179\/51247031\/lxad179.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T15:26:20Z","timestamp":1692890780000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jambio\/article\/doi\/10.1093\/jambio\/lxad179\/7240151"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,1]]},"references-count":48,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2023,8,1]]}},"URL":"https:\/\/doi.org\/10.1093\/jambio\/lxad179","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-1704501\/v1","asserted-by":"object"}]},"ISSN":["1365-2672"],"issn-type":[{"value":"1365-2672","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,8]]},"published":{"date-parts":[[2023,8,1]]},"article-number":"lxad179"}}