Function of the Pyruvate Oxidase-Lactate Oxidase Cascade in Interspecies Competition between Streptococcus oligofermentans and Streptococcus mutans

Abstract

ABSTRACTComplex interspecies interactions occur constantly between oral commensals and the opportunistic pathogenStreptococcus mutansin dental plaque. Previously, we showed that oral commensalStreptococcus oligofermentanspossesses multiple enzymes for H2O2production, especially lactate oxidase (Lox), allowing it to out-competeS. mutans. In this study, through extensive biochemical and genetic studies, we identified a pyruvate oxidase (pox) gene inS. oligofermentans. Apoxdeletion mutant completely lost Pox activity, while ectopically expressedpoxrestored activity. Pox was determined to produce most of the H2O2in the earlier growth phase and log phase, while Lox mainly contributed to H2O2production in stationary phase. Bothpoxandloxwere expressed throughout the growth phase, while expression of theloxgene increased by about 2.5-fold when cells entered stationary phase. Since lactate accumulation occurred to a large degree in stationary phase, the differential Pox- and Lox-generated H2O2can be attributed to differential gene expression and substrate availability. Interestingly, inactivation ofpoxcauses a dramatic reduction in H2O2production from lactate, suggesting a synergistic action of the two oxidases in converting lactate into H2O2. In anin vitrotwo-species biofilm experiment, thepoxmutant ofS. oligofermentansfailed to inhibitS. mutanseven thoughloxwas active. In summary,S. oligofermentansdevelops a Pox-Lox synergy strategy to maximize its H2O2formation so as to win the interspecies competition.