Dental caries (tooth-decay) is caused by biofilms harboring polymicrobial communities on teeth that leads to the onset of localized areas of enamel demineralization. Streptococcus mutans has been clinically associated with severe caries in childhood. Although commensal bacteria can combat S. mutans using self-generated antimicrobials such as hydrogen peroxide (H₂ O₂ ), constant sugar-rich diet consumption disrupts microbial homeostasis shifting toward cariogenic community. Recently, Streptococcus oralis subsp. tigurinus strain J22, an oral isolate, was identified as a uniquely potent H₂ O₂ producer. Here, we assess whether a high H₂ O₂ -producing commensal streptococcus can modulate the spatial organization and virulence of S. mutans within biofilms. Using an experimental biofilm model, we find that the presence of S. oralis J22 can effectively inhibit the clustering, accumulation, and spatial organization of S. mutans on ex vivo human tooth surface, resulting in significant reduction of enamel demineralization. Notably, the generation of H₂ O₂ via pyruvate oxidase (SpxB) from S. oralis J22 is not repressed by sugars (a common repressor in other mitis group streptococci), resulting in enhanced inhibition of S. mutans growth (vs. Streptococcus gordonii). We further investigate its impact on biofilm virulence using an in vivo rodent caries model under sugar-rich diet. Coinfection of S. mutans with S. oralis results in reduced caries development compared to either species infected alone, whereas coinfection with S. gordonii has negligible effects, suggesting that the presence of an efficient, high H₂ O₂ -producer can disrupt S. mutans virulence. This work demonstrates that oral isolates with unusual high H₂ O₂ production may be capable of modulating biofilm cariogenicity in vivo. The findings also highlight the importance of bacterial antagonistic interactions within polymicrobial communities in health and in disease-causing state.

#	Concept	H-Index	Publications	Citations
1	Engineering	2	2	354
2	Medicine	2	2	354
3	Biomedical Engineering	2	2	354
4	Cell Biology	1	1	24
5	Immunology	1	1	24

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