Ecological shifts in dental microbiome from homeostasis to dysbiosis have been hypothesized to underlie several oral diseases including dental caries. Streptococcus sanguinis, a commensal bacterium, is pivotal in maintaining oral health through its metabolic activities, including the production of ammonia and hydrogen peroxide (H2O2). This study aims to elucidate the genetic underpinnings of the glucose::phosphotransferase system (PTS) in the physiology and competitive fitness of S. sanguinis within the oral microbiome, by examining single nucleotide polymorphisms (SNPs) in the EIIABMan (manL) and HPr of PTS in S. sanguinis strain SK36. Employing genetic engineering, bioinformatic analysis, growth and metabolic assays, recreating and characterizing several unique ManL SNPs in SK36 that were identified among clinical strains of S. sanguinis. Mutations in ManL and HPr correlated with altered growth dynamics, H2O2 production, acid production, and pH homeostasis in a manner uncoupled from canonical regulators such as CcpA and Rex. These genetic variations likely contributed to S. sanguinis's competitiveness, although their ecological impact remains to be further elucidated. This research is part of the ongoing effort to understand the genetic mechanisms that contribute to microbial ecology in relation to health, knowledge from which may allow for enhanced diagnostics, pro-health formulations, and other microbial interventions.