{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:07:38Z","timestamp":1788930458996,"version":"build-2803163510"},"reference-count":33,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Guangxi Natural Science Foundation","award":["2025GXNSFAA069562"],"award-info":[{"award-number":["2025GXNSFAA069562"]}]},{"name":"\u201cDai Tu Yi Qi\u201d Project of the Key R&D Program of Guangxi","award":["GUIKE AA25069003"],"award-info":[{"award-number":["GUIKE AA25069003"]}]},{"name":"Natural Science Foundation of Guangxi","award":["2024GXNSFDA999003"],"award-info":[{"award-number":["2024GXNSFDA999003"]}]},{"name":"Guangxi Bagui Youth Talent Training Program"},{"name":"Major Intergovernmental Joint Research Project of the National Key R&D Program of China","award":["2022YFE0132700"],"award-info":[{"award-number":["2022YFE0132700"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background: Dental caries is a biofilm-associated disease in which Streptococcus mutans plays a central role. This study evaluated HT-2-1-3, a Vespidae venom-derived antimicrobial peptide, as a potential topical anti-caries lead. Methods: Candidate peptides were synthesized by Fmoc solid-phase peptide synthesis and characterized by RP-HPLC and ESI-MS. Antibacterial activity against S. mutans UA159 was assessed using MIC, MBC, growth-curve, and time-kill assays. Membrane damage, antibiofilm activity, cytocompatibility, hemolysis, and preliminary oral safety in mice were further evaluated. Results: HT-2-1-3 showed the strongest activity among the tested peptides, with MIC and MBC values of 2 \u00b5g\/mL. It inhibited bacterial growth in a concentration-dependent manner and achieved complete killing at 4\u00d7MIC (8 \u00b5g\/mL) within 2 h. Mechanistic assays showed rapid membrane depolarization, increased PI uptake, and concentration-dependent release of extracellular DNA and proteins. MD simulations further indicated that HT-2-1-3 entered the model S. mutans UA159 membrane at 1857 ns, supporting membrane permeabilization as a central component of its bactericidal activity. Scanning electron microscopy revealed dose-dependent membrane disruption, cell collapse, and rupture. HT-2-1-3 inhibited biofilm formation by approximately 58\u201363% and eradicated up to 89.0% of mature biofilms. Hemolysis remained below 4% at concentrations up to 64\u00d7MIC (128 \u00b5g\/mL), and mammalian-cell viability exceeded 95% at concentrations up to 16\u00d7MIC (32 \u00b5g\/mL). Repeated oral administration caused no obvious gingival irritation in mice. Conclusions: HT-2-1-3 showed strong bactericidal and antibiofilm activity against S. mutans UA159 and favorable preliminary biocompatibility. Its mode of action may involve membrane disruption, and it showed favorable preliminary biosafety. These findings support further optimization of HT-2-1-3 as a topical antimicrobial candidate for caries prevention and control.<\/jats:p>","DOI":"10.3390\/antibiotics15090873","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:53:28Z","timestamp":1788789208000},"page":"873","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bactericidal and Antibiofilm Activities of HT-2-1-3, a Vespidae Venom-Derived Antimicrobial Peptide, Against Streptococcus mutans UA159"],"prefix":"10.3390","volume":"15","author":[{"given":"Yangyang","family":"Chen","sequence":"first","affiliation":[{"name":"Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxiu","family":"Ye","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiurong","family":"Wu","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guolian","family":"Xu","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Wu","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiling","family":"Tang","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9358-5970","authenticated-orcid":false,"given":"Sulan","family":"Luo","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6395-4213","authenticated-orcid":false,"given":"Yong","family":"Wu","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"ref_1","unstructured":"GBD 2019 Diseases and Injuries Collaborators (2020). Global Burden of 369 Diseases and Injuries in 204 Countries and Territories, 1990\u20132019: A Systematic Analysis for the Global Burden of Disease Study 2019. Lancet, 396, 1204\u20131222."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S0140-6736(07)60031-2","article-title":"Dental caries","volume":"369","author":"Selwitz","year":"2007","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"GPP3-0051-2018","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_4","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_5","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1177\/0022034513504218","article-title":"The exopolysaccharide matrix: A virulence determinant of cariogenic biofilm","volume":"92","author":"Koo","year":"2013","journal-title":"J. Dent. Res."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Saidi, F., Bitazar, R., Bradette, N.Y., and Islam, S.T. (2022). Bacterial glycocalyx integrity impacts tolerance of Myxococcus xanthus to antibiotics and oxidative-stress agents. Biomolecules, 12.","DOI":"10.3390\/biom12040571"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"171","DOI":"10.12688\/f1000research.22499.3","article-title":"The role of salivary contents and modern technologies in the remineralization of dental enamel: A narrative review","volume":"9","author":"Farooq","year":"2020","journal-title":"F1000Research"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1139\/W10-095","article-title":"Streptococcus mutans and oral streptococci in dental plaque","volume":"57","author":"Nicolas","year":"2011","journal-title":"Can. J. Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Bin Hafeez, A., Jiang, X., Bergen, P.J., and Zhu, Y. (2021). Antimicrobial peptides: An update on classifications and databases. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111691"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1038\/nbt1267","article-title":"Antimicrobial and host-defence peptides as new anti-infective therapeutic strategies","volume":"24","author":"Hancock","year":"2006","journal-title":"Nat. Biotechnol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Mahlapuu, M., Hakansson, J., Ringstad, L., and Bjorn, C. (2016). Antimicrobial peptides: An emerging category of therapeutic agents. Front. Cell. Infect. Microbiol., 6.","DOI":"10.3389\/fcimb.2016.00194"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/nrmicro1098","article-title":"Antimicrobial peptides: Pore formers or metabolic inhibitors in bacteria?","volume":"3","author":"Brogden","year":"2005","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"105022","DOI":"10.1016\/j.archoralbio.2020.105022","article-title":"Antimicrobial peptides for the prevention and treatment of dental caries: A concise review","volume":"122","author":"Niu","year":"2021","journal-title":"Arch. Oral Biol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Zhang, O.L., Niu, J.Y., Yu, O.Y., Mei, M.L., Jakubovics, N.S., and Chu, C.H. (2023). Peptide designs for use in caries management: A systematic review. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24044247"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.actbio.2016.11.026","article-title":"Potential applications of antimicrobial peptides and their mimics in combating caries and pulpal infections","volume":"49","author":"Mai","year":"2017","journal-title":"Acta Biomater."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Hardan, L., Chedid, J.C.A., Bourgi, R., Cuevas-Suarez, C.E., Lukomska-Szymanska, M., Tosco, V., Monjaras-Avila, A.J., Jabra, M., Salloum-Yared, F., and Kharouf, N. (2023). Peptides in dentistry: A scoping review. Bioengineering, 10.","DOI":"10.3390\/bioengineering10020214"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1111\/iej.14043","article-title":"Harnessing antimicrobial peptides in endodontics","volume":"57","author":"Kong","year":"2024","journal-title":"Int. Endod. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e12887","DOI":"10.1111\/eos.12887","article-title":"Development and evaluation of a chewing gum containing antimicrobial peptide GH12 for caries prevention","volume":"130","author":"Jiang","year":"2022","journal-title":"Eur. J. Oral Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.ijantimicag.2010.08.014","article-title":"Effect of the antimicrobial decapeptide KSL on the growth of oral pathogens and Streptococcus mutans biofilm","volume":"37","author":"Liu","year":"2011","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate structure prediction of biomolecular interactions with AlphaFold 3","volume":"630","author":"Abramson","year":"2024","journal-title":"Nature"},{"key":"ref_21","first-page":"923","article-title":"Design, screening and antibacterial activity evaluation of the novel antibacterial peptide KR-1","volume":"41","author":"He","year":"2021","journal-title":"J. South. Med. Univ."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1038\/nrmicro1441","article-title":"The co-evolution of host cationic antimicrobial peptides and microbial resistance","volume":"4","author":"Peschel","year":"2006","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4818","DOI":"10.7150\/thno.73181","article-title":"Dual-sensitive antibacterial peptide nanoparticles prevent dental caries","volume":"12","author":"Zhang","year":"2022","journal-title":"Theranostics"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Zhang, O.L., Niu, J.Y., Yu, O.Y., Mei, M.L., Jakubovics, N.S., and Chu, C.H. (2023). Development of a novel peptide with antimicrobial and mineralising properties for caries management. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15112560"},{"key":"ref_25","first-page":"428","article-title":"Targeted antimicrobial self-assembly peptide hydrogel with in situ bio-mimic remineralization for caries management","volume":"44","author":"Zhou","year":"2025","journal-title":"Bioact. Mater."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1007\/s12602-011-9076-5","article-title":"Antibacterial peptides: Opportunities for the prevention and treatment of dental caries","volume":"3","author":"Pepperney","year":"2011","journal-title":"Probiotics Antimicrob. Proteins"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/psc.2836","article-title":"Advances in Fmoc solid-phase peptide synthesis","volume":"22","author":"Behrendt","year":"2016","journal-title":"J. Pept. Sci."},{"key":"ref_28","unstructured":"Clinical and Laboratory Standards Institute (2018). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically, Clinical and Laboratory Standards Institute. [11th ed.]."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"171423","DOI":"10.1016\/j.peptides.2025.171423","article-title":"Synthesis of the plant cyclotide cyO14 via the hydrazide strategy and investigation of its antibacterial and insecticidal activities","volume":"191","author":"He","year":"2025","journal-title":"Peptides"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1006\/abio.2000.4880","article-title":"Estimation of protein secondary structure from circular dichroism spectra: Comparison of CONTIN, SELCON, and CDSSTR methods with an expanded reference set","volume":"287","author":"Sreerama","year":"2000","journal-title":"Anal. Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1176934320936266","DOI":"10.1177\/1176934320936266","article-title":"A novel cecropin D-derived short cationic antimicrobial peptide exhibits antibacterial activity against wild-type and multidrug-resistant strains of Klebsiella pneumoniae and Pseudomonas aeruginosa","volume":"16","author":"Liscano","year":"2020","journal-title":"Evol. Bioinform."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1021\/acs.biochem.4c00049","article-title":"Insights into molecular interactions between a GAPDH-related fish antimicrobial peptide, analogs thereof, and bacterial membranes","volume":"63","author":"Subirade","year":"2024","journal-title":"Biochemistry"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Feoktistova, M., Geserick, P., and Leverkus, M. (2016). Crystal violet assay for determining viability of cultured cells. Cold Spring Harb. Protoc., 2016.","DOI":"10.1101\/pdb.prot087379"}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/15\/9\/873\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T04:23:19Z","timestamp":1788927799000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/15\/9\/873"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,7]]},"references-count":33,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["antibiotics15090873"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics15090873","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,7]]}}}