SpxB-mediated H2 O2 induces programmed cell death in Streptococcus sanguinis

Streptococcus sanguinis (S. sanguinis) is a commensal oral streptococci that produces hydrogen peroxide (H2 O2 ), and this production is dependent on pyruvate oxidase (SpxB) activity. In addition to its well-known role in intraspecies or interspecies competitions, recent studies have shown that H2 O2 produced by S. sanguinis under aerobic conditions not only upregulates biofilm formation and eDNA release but also regulates cell death without obvious cell lysis. Here, we report that S. sanguinis exhibits characteristic hallmarks of eukaryotic apoptosis when it encounters endogenous and exogenous H2 O2 . As the most common mode of programmed cell death (PCD), apoptosis is accompanied by a series of biochemical and morphological events, including DNA fragmentation, chromosome condensation, membrane potential depolarization, phosphatidylserine (PS) exposure, and caspase substrate binding protein activity changes. In addition, we also provide genetic evidence that there is decreased expression of the related DNA repair genes comEA, recA, dnaC, dinG, and pcrA in the wild-type compared to the isogenic spxB mutant in S. sanguinis. Our data suggest that endogenous H2 O2 is the most important agent in this development process in S. sanguinis.