Impact of Modified Lactoperoxidase Systems on Glycolytic Metabolism and Virulence Factors in Streptococcus mutans

The lactoperoxidase system (LpoS) is an enzymatic antimicrobial mechanism of saliva that oxidizes (pseudo)halide substrates to reactive compounds capable of limiting microbial growth. This study evaluated how different LpoS variants—utilizing iodide (LpoS-I−), thiocyanate (LpoS-SCN−), selenocyanate (LpoS-SeCN−), and a thiocyanate–iodide mixture (LpoS-SCN− + I−)—affect virulence, metabolism, and biofilm structure in Streptococcus mutans. Using qRT-PCR, pyruvate assays, MTT reduction, and confocal microscopy, we found that LpoS-I− most effectively reduced atpD and ldh expression, impaired acid tolerance, and decreased lactate and pyruvate production. LpoS-SCN− and LpoS-SeCN− also downregulated atpD and gtfB, although LpoS-SeCN− upregulated ldh. Despite minimal structural biofilm disruption, LpoS-I− markedly inhibited intracellular and extracellular pyruvate accumulation, suggesting altered glycolytic flux. These findings indicate that iodide-based LPO systems modulate key metabolic and regulatory pathways in S. mutans and may hold potential for inclusion in anticaries oral formulations.