Dietary Nitrite Drives Disease Outcomes in Oral Polymicrobial Infections

Abstract

<i>Streptococcus mutans</i> resides in the oral polymicrobial biofilm and is a major contributor to the development of dental caries. Interestingly, high salivary nitrite concentrations have been associated with a decreased prevalence of dental caries. Moreover, the combination of hydrogen peroxide-producing oral commensal streptococci and nitrite has been shown to mediate the generation of reactive nitrogen species, which have antimicrobial activity. The goal of this study was to examine whether nitrite affects <i>S. mutans</i> virulence during polymicrobial infections with the commensal <i>Streptococcus parasanguinis</i>. Here, we report that the combination of <i>S. parasanguinis</i> and nitrite inhibited <i>S. mutans</i> growth and biofilm formation in vitro. Glucan production, which is critical for <i>S. mutans</i> biofilm formation, was also inhibited in 2-species biofilms with <i>S. parasanguinis</i> containing nitrite as compared with biofilms that contained no nitrite. In the in vivo caries model, enamel and dentin carious lesions were significantly reduced in rats that were colonized with <i>S. parasanguinis</i> prior to infection with <i>S. mutans</i> and received nitrite in the drinking water, as compared with animals that had a single <i>S. mutans</i> infection or were co-colonized with both bacteria and received no nitrite. Last, we report that <i>S. mutans</i> LiaS, a sensor kinase of the LiaFSR 3-component system, mediates resistance to nitrosative stress. In summary, our data demonstrate that commensal streptococci and nitrite provide protection against <i>S. mutans</i> pathogenesis. Modulating nitrite concentrations in the oral cavity could be a useful strategy to combat the prevalence of dental caries.