Zirui Qin, Zhenyu Yang, Yi Zhang, Linlong Qi, Yan Peng, Shuli Deng, Yuan Wang
{"title":"生物素限制通过破坏代谢通量和毒力途径减弱变形链球菌的致病性。","authors":"Zirui Qin, Zhenyu Yang, Yi Zhang, Linlong Qi, Yan Peng, Shuli Deng, Yuan Wang","doi":"10.1159/000548822","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Our previous metagenomic analysis revealed higher frequencies of biotin-related genes (i.e., bioY, bioM, bccP) in caries-active children, indicating a potential role of biotin in caries pathogenesis. This study investigated a biotin limitation strategy against the primary cariogenic bacterium Streptococcus mutans (S. mutans), including its effects on cariogenic phenotypes, gene expression, and metabolomics.</p><p><strong>Methods: </strong>S. mutans UA159 was cultured in biotin-free medium supplemented with different biotin concentrations. The cariogenic phenotypes of the strain, including growth kinetics, biofilm formation, exopolysaccharide (EPS) production, lactate synthesis, acid/oxidative tolerance, and membrane fluidity, were measured and compared across biotin concentrations. Biofilm architecture was visualized via confocal laser-scanning microscopy (CLSM) and scanning electron microscopy (SEM). Quantitative real-time polymerase chain reaction (RT-qPCR) was employed to analyze the expression of genes associated with virulence and biotin metabolism. Metabolomic analysis was performed to characterize metabolic perturbations induced by biotin limitation in S. mutans.</p><p><strong>Results: </strong>Under biotin limitation, S. mutans exhibited significantly reduced cariogenic phenotypes, accompanied by cell elongation and reduced membrane fluidity. At the molecular level, biotin limitation suppressed the expression of key virulence-associated genes and induced a compensatory upregulation of genes involved in biotin uptake and biotin-dependent carboxylases. Metabolomic analysis under biotin-limited conditions in S. mutans revealed perturbed pathways in central carbon metabolism and nucleotide metabolism.</p><p><strong>Conclusion: </strong>Biotin limitation significantly reduced the cariogenic potential of S. mutans by disrupting metabolic flux and virulence gene expression, highlighting biotin uptake and metabolism as potential targets for anti-caries therapies.</p>","PeriodicalId":9620,"journal":{"name":"Caries Research","volume":" ","pages":"1-24"},"PeriodicalIF":2.6000,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Biotin Limitation Attenuates Streptococcus mutans Cariogenicity by Disrupting Metabolic Flux and Virulence Pathways.\",\"authors\":\"Zirui Qin, Zhenyu Yang, Yi Zhang, Linlong Qi, Yan Peng, Shuli Deng, Yuan Wang\",\"doi\":\"10.1159/000548822\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Our previous metagenomic analysis revealed higher frequencies of biotin-related genes (i.e., bioY, bioM, bccP) in caries-active children, indicating a potential role of biotin in caries pathogenesis. This study investigated a biotin limitation strategy against the primary cariogenic bacterium Streptococcus mutans (S. mutans), including its effects on cariogenic phenotypes, gene expression, and metabolomics.</p><p><strong>Methods: </strong>S. mutans UA159 was cultured in biotin-free medium supplemented with different biotin concentrations. The cariogenic phenotypes of the strain, including growth kinetics, biofilm formation, exopolysaccharide (EPS) production, lactate synthesis, acid/oxidative tolerance, and membrane fluidity, were measured and compared across biotin concentrations. Biofilm architecture was visualized via confocal laser-scanning microscopy (CLSM) and scanning electron microscopy (SEM). Quantitative real-time polymerase chain reaction (RT-qPCR) was employed to analyze the expression of genes associated with virulence and biotin metabolism. Metabolomic analysis was performed to characterize metabolic perturbations induced by biotin limitation in S. mutans.</p><p><strong>Results: </strong>Under biotin limitation, S. mutans exhibited significantly reduced cariogenic phenotypes, accompanied by cell elongation and reduced membrane fluidity. At the molecular level, biotin limitation suppressed the expression of key virulence-associated genes and induced a compensatory upregulation of genes involved in biotin uptake and biotin-dependent carboxylases. Metabolomic analysis under biotin-limited conditions in S. mutans revealed perturbed pathways in central carbon metabolism and nucleotide metabolism.</p><p><strong>Conclusion: </strong>Biotin limitation significantly reduced the cariogenic potential of S. mutans by disrupting metabolic flux and virulence gene expression, highlighting biotin uptake and metabolism as potential targets for anti-caries therapies.</p>\",\"PeriodicalId\":9620,\"journal\":{\"name\":\"Caries Research\",\"volume\":\" \",\"pages\":\"1-24\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2025-10-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Caries Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1159/000548822\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"DENTISTRY, ORAL SURGERY & MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Caries Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000548822","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DENTISTRY, ORAL SURGERY & MEDICINE","Score":null,"Total":0}
Biotin Limitation Attenuates Streptococcus mutans Cariogenicity by Disrupting Metabolic Flux and Virulence Pathways.
Introduction: Our previous metagenomic analysis revealed higher frequencies of biotin-related genes (i.e., bioY, bioM, bccP) in caries-active children, indicating a potential role of biotin in caries pathogenesis. This study investigated a biotin limitation strategy against the primary cariogenic bacterium Streptococcus mutans (S. mutans), including its effects on cariogenic phenotypes, gene expression, and metabolomics.
Methods: S. mutans UA159 was cultured in biotin-free medium supplemented with different biotin concentrations. The cariogenic phenotypes of the strain, including growth kinetics, biofilm formation, exopolysaccharide (EPS) production, lactate synthesis, acid/oxidative tolerance, and membrane fluidity, were measured and compared across biotin concentrations. Biofilm architecture was visualized via confocal laser-scanning microscopy (CLSM) and scanning electron microscopy (SEM). Quantitative real-time polymerase chain reaction (RT-qPCR) was employed to analyze the expression of genes associated with virulence and biotin metabolism. Metabolomic analysis was performed to characterize metabolic perturbations induced by biotin limitation in S. mutans.
Results: Under biotin limitation, S. mutans exhibited significantly reduced cariogenic phenotypes, accompanied by cell elongation and reduced membrane fluidity. At the molecular level, biotin limitation suppressed the expression of key virulence-associated genes and induced a compensatory upregulation of genes involved in biotin uptake and biotin-dependent carboxylases. Metabolomic analysis under biotin-limited conditions in S. mutans revealed perturbed pathways in central carbon metabolism and nucleotide metabolism.
Conclusion: Biotin limitation significantly reduced the cariogenic potential of S. mutans by disrupting metabolic flux and virulence gene expression, highlighting biotin uptake and metabolism as potential targets for anti-caries therapies.
期刊介绍：
''Caries Research'' publishes epidemiological, clinical and laboratory studies in dental caries, erosion and related dental diseases. Some studies build on the considerable advances already made in caries prevention, e.g. through fluoride application. Some aim to improve understanding of the increasingly important problem of dental erosion and the associated tooth wear process. Others monitor the changing pattern of caries in different populations, explore improved methods of diagnosis or evaluate methods of prevention or treatment. The broad coverage of current research has given the journal an international reputation as an indispensable source for both basic scientists and clinicians engaged in understanding, investigating and preventing dental disease.
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