{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T21:20:39Z","timestamp":1791840039052,"version":"4.3.4"},"reference-count":52,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,6,20]],"date-time":"2023-06-20T00:00:00Z","timestamp":1687219200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000072","name":"NIH\/NIDCR","doi-asserted-by":"publisher","award":["K23DE027412"],"award-info":[{"award-number":["K23DE027412"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"NIH\/NIDCR","doi-asserted-by":"publisher","award":["R01DE031025"],"award-info":[{"award-number":["R01DE031025"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Dental caries is one of the most common chronic diseases worldwide. Streptococcus mutans and Candida albicans are two major pathogens associated with dental caries. Several recent studies revealed that Lactobacillus plantarum inhibits S. mutans and C. albicans in biofilms and in a rodent model of dental caries. The aim of this study was to investigate the dose-dependent effect of L. plantarum against S. mutans and C. albicans in a planktonic model that simulated a high-caries-risk clinical condition. Mono-, dual-, and multi-species models were utilized, with five doses of L. plantarum (ranging from 1.0 \u00d7 104 to 1.0 \u00d7 108 CFU\/mL). Real-time PCR was used to assess the expression of the virulence genes of C. albicans and S. mutans and the genes of L. plantarum. Student\u2019s t-tests and one-way ANOVA, followed by post hoc tests, were employed to compare the cell viability and gene expression among groups. A dose-dependent inhibition on C. albicans and S. mutans was observed with increased dosages of L. plantarum. L. plantarum at 108 CFU\/mL demonstrated the highest antibacterial and antifungal inhibitory effect in the dual- and multi-species models. Specifically, at 20 h, the growth of C. albicans and S. mutans was suppressed by 1.5 and 5 logs, respectively (p &lt; 0.05). The antifungal and antibacterial effects were attenuated in lower doses of L. plantarum (104\u2013107 CFU\/mL). The expression of C. albicans\u00a0HWP1 and ECE 1 genes and S. mutans\u00a0lacC and lacG genes were significantly downregulated with an added 108 CFU\/mL of L. plantarum (p &lt; 0.05). The addition of 108 CFU\/mL L. plantarum further inhibited the hyphae or pseudohyphae formation of C. albicans. In summary, L. plantarum demonstrated dose-dependent antifungal and antibacterial effects against C. albicans and S. mutans. L. plantarum emerged as a promising candidate for the creation of novel antimicrobial probiotic products targeting dental caries prevention. Further research is warranted to identify the functional metabolites produced by L. plantarum at different dosages when interacting with C. albicans and S. mutans.<\/jats:p>","DOI":"10.3390\/pathogens12060848","type":"journal-article","created":{"date-parts":[[2023,6,20]],"date-time":"2023-06-20T02:26:56Z","timestamp":1687228016000},"page":"848","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Dose-Dependent Inhibitory Effect of Probiotic Lactobacillus plantarum on Streptococcus mutans-Candida albicans Cross-Kingdom Microorganisms"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6739-0806","authenticated-orcid":false,"given":"Jianhang","family":"Bao","sequence":"first","affiliation":[{"name":"Eastman Institute for Oral Health, University of Rochester Medical Center, Rochester, NY 14642, USA"},{"name":"School of Stomatology, Henan University, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyan","family":"Huang","sequence":"additional","affiliation":[{"name":"Eastman Institute for Oral Health, University of Rochester Medical Center, Rochester, NY 14642, USA"},{"name":"School of Stomatology, Henan University, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zeng","sequence":"additional","affiliation":[{"name":"Eastman Institute for Oral Health, University of Rochester Medical Center, Rochester, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong Tong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0976-4655","authenticated-orcid":false,"given":"Xingyi","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gina","family":"Meng","sequence":"additional","affiliation":[{"name":"School of Arts and Science, University of Rochester, Rochester, NY 14627, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6428-2252","authenticated-orcid":false,"given":"Yanfang","family":"Ren","sequence":"additional","affiliation":[{"name":"Eastman Institute for Oral Health, University of Rochester Medical Center, Rochester, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Xiao","sequence":"additional","affiliation":[{"name":"Eastman Institute for Oral Health, University of Rochester Medical Center, Rochester, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1177\/0022034520908533","article-title":"Global, Regional, and National Levels and Trends in Burden of Oral Conditions from 1990 to 2017: A Systematic Analysis for the Global Burden of Disease 2017 Study","volume":"99","author":"Bernabe","year":"2020","journal-title":"J. Dent. Res."},{"key":"ref_2","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_3","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1177\/154405910608501002","article-title":"The role of sucrose in cariogenic dental biofilm formation\u2014New insight","volume":"85","author":"Koo","year":"2006","journal-title":"J. Dent. Res."},{"key":"ref_4","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_5","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_6","doi-asserted-by":"crossref","first-page":"61","DOI":"10.3109\/00016359009012735","article-title":"Etiology, pathogenesis, therapy, and prophylaxis of oral yeast infections","volume":"48","year":"1990","journal-title":"Acta Odontol. Scand."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1159\/000481833","article-title":"Candida albicans and Early Childhood Caries: A Systematic Review and Meta-Analysis","volume":"52","author":"Xiao","year":"2018","journal-title":"Caries Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1159\/000324809","article-title":"Dental caries in rats associated with Candida albicans","volume":"45","author":"Klinke","year":"2011","journal-title":"Caries Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1038\/s41396-020-00823-8","article-title":"Candida albicans promotes tooth decay by inducing oral microbial dysbiosis","volume":"15","author":"Du","year":"2021","journal-title":"ISME J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1177\/0022034515592859","article-title":"Binding Force Dynamics of Streptococcus mutans-glucosyltransferase B to Candida albicans","volume":"94","author":"Hwang","year":"2015","journal-title":"J. Dent. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1968","DOI":"10.1128\/IAI.00087-14","article-title":"Symbiotic Relationship between Streptococcus mutans and Candida albicans Synergizes Virulence of Plaque Biofilms In Vivo","volume":"82","author":"Falsetta","year":"2014","journal-title":"Infect. Immun."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Metwalli, K.H., Khan, S.A., Krom, B.P., and Jabra-Rizk, M.A. (2013). Streptococcus mutans, Candida albicans, and the human mouth: A sticky situation. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003616"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6357","DOI":"10.1128\/AEM.05203-11","article-title":"Role of glucosyltransferase B in interactions of Candida albicans with Streptococcus mutans and with an experimental pellicle on hydroxyapatite surfaces","volume":"77","author":"Gregoire","year":"2011","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"7061587","DOI":"10.1155\/2016\/7061587","article-title":"Comparison of Antimicrobial Activity of Chlorhexidine, Coconut Oil, Probiotics, and Ketoconazole on Candida albicans Isolated in Children with Early Childhood Caries: An In Vitro Study","volume":"2016","author":"Shino","year":"2016","journal-title":"Scientifica"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Aljaffary, M., Jang, H., Alomeir, N., Zeng, Y., Alkhars, N., Vasani, S., Almulhim, A., Wu, T.T., Quataert, S., and Bruno, J. (2023). Effects of Nystatin oral rinse on oral Candida species and Streptococcus mutans among healthy adults. Clin. Oral Investig.","DOI":"10.1007\/s00784-023-04969-5"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"105582","DOI":"10.1016\/j.archoralbio.2022.105582","article-title":"Effect of Nystatin on Candida albicans-Streptococcus mutans duo-species biofilms","volume":"145","author":"Alomeir","year":"2023","journal-title":"Arch. Oral Biol."},{"key":"ref_17","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_18","unstructured":"FAOD, and WHO (2001). Food and Agriculture Organization of the United Nations and World Health Organization Expert Consultation Report, Cordoba, Argentina, Food and Agriculture Organization of the United Nations."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Markowiak, P., and \u015ali\u017cewska, K. (2017). Effects of Probiotics, Prebiotics, and Synbiotics on Human Health. Nutrients, 9.","DOI":"10.3390\/nu9091021"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/0168-6445(93)90057-G","article-title":"Genetics of bacteriocins produced by lactic acid bacteria","volume":"12","author":"Klaenhammer","year":"1993","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"19203","DOI":"10.1038\/s41598-020-76171-6","article-title":"Characterization of transcriptional response of Lactobacillus plantarum under acidic conditions provides insight into bacterial adaptation in fermentative environments","volume":"10","author":"Jung","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1177\/0022034518790941","article-title":"Association between Oral Candida and Bacteriome in Children with Severe ECC","volume":"97","author":"Xiao","year":"2018","journal-title":"J. Dent. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4345804","DOI":"10.1155\/2020\/4345804","article-title":"Inhibitory Effect of Lactobacillus plantarum CCFM8724 towards Streptococcus mutans- and Candida albicans-Induced Caries in Rats","volume":"2020","author":"Zhang","year":"2020","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"774","DOI":"10.3389\/fmicb.2020.00774","article-title":"Inhibition of Biofilm Formation and Virulence by K41 Isolated From Traditional Sichuan Pickles","volume":"11","author":"Zhang","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Srivastava, N., Ellepola, K., Venkiteswaran, N., Chai, L.Y.A., Ohshima, T., and Seneviratne, C.J. (2020). Lactobacillus Plantarum 108 Inhibits Streptococcus mutans and Candida albicans Mixed-Species Biofilm Formation. Antibiotics, 9.","DOI":"10.3390\/antibiotics9080478"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.joen.2018.12.007","article-title":"Lactobacillus plantarum Lipoteichoic Acid Inhibits Oral Multispecies Biofilm","volume":"45","author":"Kim","year":"2019","journal-title":"J. Endod."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1111\/jcmm.13496","article-title":"Probiotic Lactobacillus sp. inhibit growth, biofilm formation and gene expression of caries-inducing Streptococcus mutans","volume":"22","author":"Wasfi","year":"2018","journal-title":"J. Cell. Mol. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"872012","DOI":"10.3389\/fcimb.2022.872012","article-title":"Lactobacillus plantarum Disrupts S. mutans\u2013C. albicans Cross-Kingdom Biofilms","volume":"12","author":"Zeng","year":"2022","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Hassl\u00f6f, P., Hedberg, M., Twetman, S., and Stecks\u00e9n-Blicks, C. (2010). Growth inhibition of oral mutans streptococci and candida by commercial probiotic lactobacilli\u2014An in vitro study. BMC Oral Health, 10.","DOI":"10.1186\/1472-6831-10-18"},{"key":"ref_30","first-page":"127","article-title":"Inhibitory effect of Lactobacillus plantarum CCFM8724 on caries-causing dual biofilms","volume":"46","author":"Qiuxiang","year":"2020","journal-title":"Food Ferment. Ind."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Zeng, Y., Fadaak, A., Alomeir, N., Wu, Y., Wu, T.T., Qing, S., and Xiao, J. (2023). Effect of Probiotic Lactobacillus plantarum on Streptococcus mutans and Candida albicans Clinical Isolates from Children with Early Childhood Caries. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032991"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Huang, X., Bao, J., Zeng, Y., Meng, G., Lu, X., Wu, T.T., Ren, Y., and Xiao, J. (2023). Anti-cariogenic Properties of Lactobacillus plantarum in the Utilization of Galacto-Oligosaccharide. Nutrients, 15.","DOI":"10.3390\/nu15092017"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1177\/00220345211012385","article-title":"Oral Candida Predicts Streptococcus mutans Emergence in Underserved US Infants","volume":"101","author":"Alkhars","year":"2022","journal-title":"J. Dent. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/nprot.2008.73","article-title":"Analyzing real-time PCR data by the comparative C(T) method","volume":"3","author":"Schmittgen","year":"2008","journal-title":"Nat. Protoc."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1002\/fsn3.1025","article-title":"Characterization of antimicrobial activity of three Lactobacillus plantarum strains isolated from Chinese traditional dairy food","volume":"7","author":"Hu","year":"2019","journal-title":"Food Sci. Nutr."},{"key":"ref_36","first-page":"3265","article-title":"Effect of Acetic Acid and Lactic Acid at Low pH in Growth and Azole Resistance of Candida albicans and Candida glabrata","volume":"9","author":"Pedro","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1007\/s00217-009-1179-9","article-title":"Production of organic acids by Lactobacillus strains in three different media","volume":"230","year":"2010","journal-title":"Eur. Food Res. Technol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1964277","DOI":"10.1080\/20002297.2021.1964277","article-title":"Profuse diversity and acidogenicity of the candida-biome of deep carious lesions of Severe Early Childhood Caries (S-ECC)","volume":"13","author":"Fakhruddin","year":"2021","journal-title":"J. Oral Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1159\/000204911","article-title":"Acid Production by Oral Strains of Candida albicans and Lactobacilli","volume":"43","author":"Klinke","year":"2009","journal-title":"Caries Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1111\/odi.12691","article-title":"Is the oral fungal pathogen Candida albicans a cariogen?","volume":"24","author":"Pereira","year":"2018","journal-title":"Oral Dis."},{"key":"ref_41","first-page":"44","article-title":"Taxonomy of Lactobacilli and Bifidobacteria","volume":"8","author":"Felis","year":"2007","journal-title":"Curr. Issues Intest. Microbiol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Liang, J., Zhou, Y., Tang, G., Wu, R., and Lin, H. (2023). Exploration of the Main Antibiofilm Substance of Lactobacillus plantarum ATCC 14917 and Its Effect against Streptococcus mutans. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24031986"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.1016\/j.peptides.2009.05.014","article-title":"An overview of the mosaic bacteriocin pln loci from Lactobacillus plantarum","volume":"30","author":"Diep","year":"2009","journal-title":"Peptides"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1046\/j.1365-2958.2003.03310.x","article-title":"Inducible bacteriocin production in Lactobacillus is regulated by differential expression of the pln operons and by two antagonizing response regulators, the activity of which is enhanced upon phosphorylation","volume":"47","author":"Diep","year":"2003","journal-title":"Mol. Microbiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1002\/(SICI)1097-0061(199805)14:7<681::AID-YEA256>3.0.CO;2-8","article-title":"Genetic organization and sequence analysis of the hypha-specific cell wall protein gene HWP1 of Candida albicans","volume":"14","author":"Staab","year":"1998","journal-title":"Yeast"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3648","DOI":"10.1128\/iai.61.9.3648-3655.1993","article-title":"Cloning and characterization of ECE1, a gene expressed in association with cell elongation of the dimorphic pathogen Candida albicans","volume":"61","author":"Birse","year":"1993","journal-title":"Infect. Immun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5273","DOI":"10.1128\/JB.181.17.5273-5279.1999","article-title":"HWP1 functions in the morphological development of Candida albicans downstream of EFG1, TUP1, and RBF1","volume":"181","author":"Sharkey","year":"1999","journal-title":"J. Bacteriol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1126\/science.283.5407.1535","article-title":"Adhesive and mammalian transglutaminase substrate properties of Candida albicans Hwp1","volume":"283","author":"Staab","year":"1999","journal-title":"Science"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Martin, R., Albrecht-Eckardt, D., Brunke, S., Hube, B., H\u00fcnniger, K., and Kurzai, O. (2013). A core filamentation response network in Candida albicans is restricted to eight genes. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0058613"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/s00294-015-0540-8","article-title":"Environmental pH adaption and morphological transitions in Candida albicans","volume":"62","author":"Du","year":"2016","journal-title":"Curr. Genet."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1111\/j.1462-5822.2008.01198.x","article-title":"Candida albicans transcription factor Rim101 mediates pathogenic interactions through cell wall functions","volume":"10","author":"Nobile","year":"2008","journal-title":"Cell. Microbiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3322","DOI":"10.1099\/mic.0.031591-0","article-title":"Global transcriptional analysis of acid-inducible genes in Streptococcus mutans: Multiple two-component systems involved in acid adaptation","volume":"155","author":"Gong","year":"2009","journal-title":"Microbiology"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/12\/6\/848\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:56:51Z","timestamp":1760126211000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/12\/6\/848"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,20]]},"references-count":52,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["pathogens12060848"],"URL":"https:\/\/doi.org\/10.3390\/pathogens12060848","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,20]]}}}