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School of Medicine","award":["KQYJXK2020"],"award-info":[{"award-number":["KQYJXK2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Dental caries is a chronic disease resulting from dysbiosis in the oral microbiome. Antagonism of commensal Streptococcus sanguinis and Streptococcus gordonii against cariogenic Streptococcus mutans is pivotal to keep the microecological balance. However, concerns are growing on antimicrobial agents in anticaries therapy, for broad spectrum antimicrobials may have a profound impact on the oral microbial community, especially on commensals. Here, we report celastrol, extracted from Traditional Chinese Medicine\u2019s Tripterygium wilfordii (TW) plant, as a promising anticaries candidate. Our results revealed that celastrol showed antibacterial and antibiofilm activity against cariogenic bacteria S. mutans while exhibiting low cytotoxicity. By using a multispecies biofilm formed by S. mutans UA159, S. sanguinis SK36, and S. gordonii DL1, we observed that even at relatively low concentrations, celastrol reduced S. mutans proportion and thereby inhibited lactic acid production as well as water-insoluble glucan formation. We found that celastrol thwarted S. mutans outgrowth through the activation of pyruvate oxidase (SpxB) and H2O2-dependent antagonism between commensal oral streptococci and S. mutans. Our data reveal new anticaries properties of celastrol that enhance oral streptococcal antagonism, which thwarts S. mutans outgrowth, indicating its potential to maintain oral microbial balance for prospective anticaries therapy.<\/jats:p>","DOI":"10.3390\/antibiotics12081245","type":"journal-article","created":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T01:28:46Z","timestamp":1690766926000},"page":"1245","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Anticariogenic Activity of Celastrol and Its Enhancement of Streptococcal Antagonism in Multispecies Biofilm"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6019-057X","authenticated-orcid":false,"given":"Hao","family":"Li","sequence":"first","affiliation":[{"name":"Department of Endodontics, Shanghai Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, 500 Quxi Road, Shanghai 200011, China"},{"name":"National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, No. 639, Zhizaoju Road, Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenguang","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Endodontics, Shanghai Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, 500 Quxi Road, Shanghai 200011, China"},{"name":"National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, No. 639, Zhizaoju Road, Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyuan","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Endodontics, Shanghai Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, 500 Quxi Road, Shanghai 200011, China"},{"name":"National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, No. 639, Zhizaoju Road, Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengwei","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Endodontics, Shanghai Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, 500 Quxi Road, Shanghai 200011, China"},{"name":"National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, No. 639, Zhizaoju Road, Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Endodontics, Shanghai Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, 500 Quxi Road, Shanghai 200011, China"},{"name":"National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, No. 639, Zhizaoju Road, Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17030","DOI":"10.1038\/nrdp.2017.30","article-title":"Dental caries","volume":"3","author":"Pitts","year":"2017","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S94","DOI":"10.1111\/jcpe.12677","article-title":"Global epidemiology of dental caries and severe periodontitis\u2014A comprehensive review","volume":"44","author":"Frencken","year":"2017","journal-title":"J. Clin. Periodontol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1038\/s41579-018-0089-x","article-title":"The oral microbiota: Dynamic communities and host interactions","volume":"16","author":"Lamont","year":"2018","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1177\/0022034517736498","article-title":"Rebalancing the Caries Microbiome Dysbiosis: Targeted Treatment and Sugar Alcohols","volume":"29","author":"Zhan","year":"2018","journal-title":"Adv. Dent. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1177\/0022034517736496","article-title":"The Caries Microbiome: Implications for Reversing Dysbiosis","volume":"29","author":"Tanner","year":"2018","journal-title":"Adv. Dent. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1016\/j.csbj.2021.02.010","article-title":"The oralome and its dysbiosis: New insights into oral microbiome-host interactions","volume":"19","author":"Radaic","year":"2021","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1038\/s41396-020-0592-8","article-title":"Pyruvate secretion by oral streptococci modulates hydrogen peroxide dependent antagonism","volume":"14","author":"Redanz","year":"2020","journal-title":"ISME J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"915","DOI":"10.2217\/fmb-2018-0043","article-title":"Streptococcus sanguinis biofilm formation & interaction with oral pathogens","volume":"13","author":"Zhu","year":"2018","journal-title":"Future Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1111\/j.1574-6941.2008.00585.x","article-title":"Role of hydrogen peroxide in competition and cooperation between Streptococcus gordonii and Actinomyces naeslundii","volume":"66","author":"Jakubovics","year":"2008","journal-title":"FEMS Microbiol. Ecol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S12","DOI":"10.1111\/jcpe.12679","article-title":"Dental biofilm: Ecological interactions in health and disease","volume":"44","author":"Marsh","year":"2017","journal-title":"J. Clin. Periodontol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1128\/microbiolspec.GPP3-0051-2018","article-title":"The Biology of Streptococcus mutans","volume":"7","author":"Lemos","year":"2019","journal-title":"Microbiol. Spectr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1177\/0022034517736497","article-title":"Therapeutic Strategies Targeting Cariogenic Biofilm Microenvironment","volume":"29","author":"Liu","year":"2018","journal-title":"Adv. Dent. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s10096-013-1993-7","article-title":"The virulence of Streptococcus mutans and the ability to form biofilms","volume":"33","author":"Jurczak","year":"2014","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e00529-19","DOI":"10.1128\/mSystems.00529-19","article-title":"Metabolic Modeling of Streptococcus mutans Reveals Complex Nutrient Requirements of an Oral Pathogen","volume":"4","author":"Jijakli","year":"2019","journal-title":"mSystems"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"290","DOI":"10.3390\/nu2030290","article-title":"Streptococcus mutans, Caries and Simulation Models","volume":"2","author":"Forssten","year":"2010","journal-title":"Nutrients"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.tim.2017.09.008","article-title":"Oral Biofilms: Pathogens, Matrix, and Polymicrobial Interactions in Microenvironments","volume":"26","author":"Bowen","year":"2018","journal-title":"Trends Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3024","DOI":"10.1128\/JB.01649-09","article-title":"Exopolysaccharides produced by Streptococcus mutans glucosyltransferases modulate the establishment of microcolonies within multispecies biofilms","volume":"192","author":"Koo","year":"2010","journal-title":"J. Bacteriol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"41332","DOI":"10.1038\/srep41332","article-title":"Candida albicans stimulates Streptococcus mutans microcolony development via cross-kingdom biofilm-derived metabolites","volume":"7","author":"Kim","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"900918","DOI":"10.3389\/fcimb.2022.900918","article-title":"Dental Materials for Oral Microbiota Dysbiosis: An Update","volume":"12","author":"Zhu","year":"2022","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1177\/0022034519880157","article-title":"Microbial Interactions in Oral Communities Mediate Emergent Biofilm Properties","volume":"99","author":"Diaz","year":"2020","journal-title":"J. Dent. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5658212","DOI":"10.1155\/2020\/5658212","article-title":"Application of Antibiotics\/Antimicrobial Agents on Dental Caries","volume":"2020","author":"Qiu","year":"2020","journal-title":"Biomed. Res. Int."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1177\/0022034517709739","article-title":"Developing a New Generation of Antimicrobial and Bioactive Dental Resins","volume":"96","author":"Cheng","year":"2017","journal-title":"J. Dent. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"563","DOI":"10.3390\/antibiotics12030563","article-title":"Novel Lactotransferrin-Derived Antimicrobial Peptide LF-1 Inhibits the Cariogenic Virulence Factors of Streptococcus mutans","volume":"12","author":"Luo","year":"2023","journal-title":"Antibiotics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"103768","DOI":"10.1016\/j.jdent.2021.103768","article-title":"Effects of chlorhexidine mouthwash on the oral microbiome","volume":"113","author":"Brookes","year":"2021","journal-title":"J. Dent."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1038\/s41396-020-00832-7","article-title":"Ecology and evolution of antimicrobial resistance in bacterial communities","volume":"15","author":"Bottery","year":"2021","journal-title":"ISME J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41522-020-0124-3","article-title":"Oral biofilms exposure to chlorhexidine results in altered microbial composition and metabolic profile","volume":"6","author":"Chatzigiannidou","year":"2020","journal-title":"NPJ Biofilms Microbiomes"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"69","DOI":"10.3389\/fmed.2017.00069","article-title":"Celastrol: A Spectrum of Treatment Opportunities in Chronic Diseases","volume":"4","author":"Cascao","year":"2017","journal-title":"Front. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1742-2094-7-17","article-title":"Reduction of \u03b2-amyloid pathology by celastrol in a transgenic mouse model of Alzheimer\u2019s disease","volume":"7","author":"Paris","year":"2010","journal-title":"J. Neuroinflamm."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"ftw059","DOI":"10.1093\/femspd\/ftw059","article-title":"Control of autoimmune inflammation by celastrol, a natural triterpenoid","volume":"74","author":"Venkatesha","year":"2016","journal-title":"Pathog. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"558741","DOI":"10.3389\/fphar.2020.558741","article-title":"Celastrol: A Review of Useful Strategies Overcoming its Limitation in Anticancer Application","volume":"11","author":"Shi","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"11144","DOI":"10.1021\/acs.jmedchem.8b01224","article-title":"Celastrol Promotes Weight Loss in Diet-Induced Obesity by Inhibiting the Protein Tyrosine Phosphatases PTP1B and TCPTP in the Hypothalamus","volume":"61","author":"Kyriakou","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Padilla-Montano, N., de Leon Guerra, L., and Moujir, L. (2021). Antimicrobial Activity and Mode of Action of Celastrol, a Nortriterpen Quinone Isolated from Natural Sources. Foods, 10.","DOI":"10.3390\/foods10030591"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e03699-22","DOI":"10.1128\/spectrum.03699-22","article-title":"Antibacterial Activity of an FtsZ Inhibitor Celastrol and Its Synergistic Effect with Vancomycin against Enterococci In Vitro and In Vivo","volume":"11","author":"Lu","year":"2023","journal-title":"Microbiol. Spectr."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Yehia, F.A.A., Yousef, N., and Askoura, M. (2022). Celastrol mitigates staphyloxanthin biosynthesis and biofilm formation in Staphylococcus aureus via targeting key regulators of virulence; in vitro and in vivo approach. BMC Microbiol., 22.","DOI":"10.1186\/s12866-022-02515-z"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1177\/0022034517746371","article-title":"Novel Anticaries and Remineralization Agents: Future Research Needs","volume":"97","author":"Featherstone","year":"2018","journal-title":"J. Dent. Res."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Relucenti, M., Familiari, G., Donfrancesco, O., Taurino, M., Li, X., Chen, R., Artini, M., Papa, R., and Selan, L. (2021). Microscopy Methods for Biofilm Imaging: Focus on SEM and VP-SEM Pros and Cons. Biology, 10.","DOI":"10.3390\/biology10010051"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/s41589-021-00745-2","article-title":"Mutanofactin promotes adhesion and biofilm formation of cariogenic Streptococcus mutans","volume":"17","author":"Li","year":"2021","journal-title":"Nat. Chem. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1111\/omi.12231","article-title":"Live and let die: Hydrogen peroxide production by the commensal flora and its role in maintaining a symbiotic microbiome","volume":"33","author":"Redanz","year":"2018","journal-title":"Mol. Oral Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1159\/000484985","article-title":"Ecological Approaches to Dental Caries Prevention: Paradigm Shift or Shibboleth?","volume":"52","author":"Philip","year":"2018","journal-title":"Caries Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2413","DOI":"10.3390\/microorganisms10122413","article-title":"Oral Microorganisms and Biofilms: New Insights to Defeat the Main Etiologic Factor of Oral Diseases","volume":"10","author":"Bertolini","year":"2022","journal-title":"Microorganisms"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1177\/0022034515571416","article-title":"Effect of antibacterial dental adhesive on multispecies biofilms formation","volume":"94","author":"Zhang","year":"2015","journal-title":"J. Dent. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1177\/0022034514561259","article-title":"Combinatorial effects of arginine and fluoride on oral bacteria","volume":"94","author":"Zheng","year":"2015","journal-title":"J. Dent. Res."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Chen, H., Yang, Y., Weir, M.D., Dai, Q., Lei, L., Homayounfar, N., Oates, T.W., Yang, K., Zhang, K., and Hu, T. (2020). Regulating Oral Biofilm from Cariogenic State to Non-Cariogenic State via Novel Combination of Bioactive Therapeutic Composite and Gene-Knockout. Microorganisms, 8.","DOI":"10.3390\/microorganisms8091410"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1159\/000479091","article-title":"Diversity in Antagonistic Interactions between Commensal Oral Streptococci and Streptococcus mutans","volume":"52","author":"Huang","year":"2018","journal-title":"Caries Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e00257-22","DOI":"10.1128\/jb.00257-22","article-title":"Oral Commensal Streptococci: Gatekeepers of the Oral Cavity","volume":"204","author":"Baty","year":"2022","journal-title":"J. Bacteriol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/j.micres.2009.12.004","article-title":"Antibacterial properties of zeylasterone, a triterpenoid isolated from Maytenus blepharodes, against Staphylococcus aureus","volume":"165","author":"Moujir","year":"2010","journal-title":"Microbiol. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"543","DOI":"10.2478\/s11535-010-0045-x","article-title":"Antibacterial activity of oleanolic and ursolic acids and their derivatives","volume":"5","author":"Wolska","year":"2010","journal-title":"Open Life Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"m2795","DOI":"10.1136\/bmj.m2795","article-title":"COVID-19: Disinfectants and sanitisers are changing microbiomes","volume":"370","author":"Singh","year":"2020","journal-title":"BMJ"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"185","DOI":"10.2174\/1874210601004010185","article-title":"Influence of individual saliva secretion on fluoride bioavailability","volume":"4","author":"Naumova","year":"2010","journal-title":"Open Dent. J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1146\/annurev.nu.04.070184.000555","article-title":"Dietary intake and bioavailability of fluoride","volume":"4","author":"Rao","year":"1984","journal-title":"Ann. Rev. Nutr."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/s42003-018-0041-7","article-title":"Ecology determines how low antibiotic concentration impacts community composition and horizontal transfer of resistance genes","volume":"1","author":"Cairns","year":"2018","journal-title":"Commun. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e00291-16","DOI":"10.1128\/mSphere.00291-16","article-title":"Biological and Chemical Adaptation to Endogenous Hydrogen Peroxide Production in Streptococcus pneumoniae D39","volume":"2","author":"Lisher","year":"2017","journal-title":"mSphere"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e0043921","DOI":"10.1128\/JB.00439-21","article-title":"Pyruvate Oxidase as a Key Determinant of Pneumococcal Viability during Transcytosis across Brain Endothelium","volume":"203","author":"Anil","year":"2021","journal-title":"J. Bacteriol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"6815","DOI":"10.1128\/JB.185.23.6815-6825.2003","article-title":"Factors contributing to hydrogen peroxide resistance in Streptococcus pneumoniae include pyruvate oxidase (SpxB) and avoidance of the toxic effects of the fenton reaction","volume":"185","author":"Pericone","year":"2003","journal-title":"J. Bacteriol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"6793957","DOI":"10.1155\/2019\/6793957","article-title":"Prooxidative Activity of Celastrol Induces Apoptosis, DNA Damage, and Cell Cycle Arrest in Drug-Resistant Human Colon Cancer Cells","volume":"2019","author":"Moreira","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/s41392-022-01231-4","article-title":"Celastrol suppresses colorectal cancer via covalent targeting peroxiredoxin 1","volume":"8","author":"Xu","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"10290","DOI":"10.7150\/thno.46728","article-title":"Celastrol induces ROS-mediated apoptosis via directly targeting peroxiredoxin-2 in gastric cancer cells","volume":"10","author":"Chen","year":"2020","journal-title":"Theranostics"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4121","DOI":"10.1128\/JCM.01232-10","article-title":"Bacterial 16S sequence analysis of severe caries in young permanent teeth","volume":"48","author":"Gross","year":"2010","journal-title":"J. Clin. Microbiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1177\/0022034512442894","article-title":"Streptococcus mutans out-competes Streptococcus gordonii in vivo","volume":"91","author":"Tanzer","year":"2012","journal-title":"J. Dent. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.1021\/acs.jnatprod.0c00067","article-title":"Synthesis and Biological Evaluation of Celastrol Derivatives as Potential Immunosuppressive Agents","volume":"83","author":"He","year":"2020","journal-title":"J. Nat. Prod."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"113936","DOI":"10.1016\/j.molliq.2020.113936","article-title":"Enhanced solubility, stability, permeation and anti-cancer efficacy of Celastrol-\u03b2-cyclodextrin inclusion complex","volume":"318","author":"Shukla","year":"2020","journal-title":"J. Mol. Liq."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1016\/j.dental.2017.07.001","article-title":"Do quaternary ammonium monomers induce drug resistance in cariogenic, endodontic and periodontal bacterial species?","volume":"33","author":"Wang","year":"2017","journal-title":"Dent. Mater."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1177\/0022034520936639","article-title":"pH-Responsive Antibacterial Resin Adhesives for Secondary Caries Inhibition","volume":"99","author":"Liang","year":"2020","journal-title":"J. Dent. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1016\/j.dental.2021.08.002","article-title":"Intelligent pH-responsive dental sealants to prevent long-term microleakage","volume":"37","author":"Li","year":"2021","journal-title":"Dent. Mater."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3102","DOI":"10.3389\/fmicb.2019.03102","article-title":"Resumptive Streptococcus mutans Persisters Induced From Dimethylaminododecyl Methacrylate Elevated the Cariogenic Virulence by Up-Regulating the Quorum-Sensing and VicRK Pathway Genes","volume":"10","author":"Lu","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4438","DOI":"10.1128\/JCM.41.9.4438-4441.2003","article-title":"Development of a 5\u2032 nuclease-based real-time PCR assay for quantitative detection of cariogenic dental pathogens Streptococcus mutans and Streptococcus sobrinus","volume":"41","author":"Yoshida","year":"2003","journal-title":"J. Clin. Microbiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3827","DOI":"10.1128\/JCM.42.8.3827-3830.2004","article-title":"Real-time TaqMan PCR for quantifying oral bacteria during biofilm formation","volume":"42","author":"Suzuki","year":"2004","journal-title":"J. Clin. Microbiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1177\/0022034520912181","article-title":"Magnesium-Dependent Promotion of H2O2 Production Increases Ecological Competitiveness of Oral Commensal Streptococci","volume":"99","author":"Cheng","year":"2020","journal-title":"J. Dent. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e01697-17","DOI":"10.1128\/AEM.01697-17","article-title":"Plasticity of the Pyruvate Node Modulates Hydrogen Peroxide Production and Acid Tolerance in Multiple Oral Streptococci","volume":"84","author":"Cheng","year":"2018","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"8025","DOI":"10.1128\/AEM.06362-11","article-title":"Cloning-independent and counterselectable markerless mutagenesis system in Streptococcus mutans","volume":"77","author":"Xie","year":"2011","journal-title":"Appl. Environ. Microbiol."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/12\/8\/1245\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:21:41Z","timestamp":1760127701000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/12\/8\/1245"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,28]]},"references-count":70,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["antibiotics12081245"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics12081245","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,28]]}}}