SummaryThe oral microbial flora contains over 500 different microbial species that often interact as a means to compete for limited space and nutritional resources. Streptococcus mutans, a major caries-causing pathogen, is a species which tends to interact competitively with other species in the oral cavity, largely due to its ability to generate copious quantities of the toxic metabolite, lactic acid. However, during a recent clinical study, we discovered a novel oral streptococcal species, Streptococcus oligofermentans, whose abundance appeared to be inversely correlated with that of S. mutans within dental plaque samples and thus suggested a possible antagonistic relationship with S. mutans. In this study, we used a defined in vitro interspecies interaction assay to confirm that S. oligofermentans was indeed able to inhibit the growth of S. mutans. Interestingly, this inhibitory effect was relatively specific to S. mutans and was actually enhanced by the presence of lactic acid. Biochemical analyses revealed that S. oligofermentans inhibited the growth of S. mutans via the production of hydrogen peroxide with lactic acid as the substrate. Further genetic and molecular analysis led to the discovery of the lactate oxidase (lox) gene of S. oligofermentans as responsible for this biological activity.Consequently, the lox mutant of S. oligofermentans also showed dramatically reduced inhibitory effects against S. mutans and also exhibited greatly impaired growth in the presence of the lactate produced by S. mutans. These data indicate that S. oligofermentans possesses the capacity to convert its competitor's main 'weapon' (lactic acid) into an inhibitory chemical (H 2O2) in order to gain a competitive growth advantage. This fascinating ability may be an example of a counteroffensive strategy used during chemical warfare within the oral microbial community.

We previously demonstrated that Streptococcus oligofermentans suppressed the growth of Streptococcus mutans, the primary cariogenic pathogen, by producing hydrogen peroxide (H 2 O 2 ) through lactate oxidase activity. In this study, we found that the lox mutant of S. oligofermentans regained the inhibition while growing on peptone-rich plates.