Molecular Mechanisms Controlling Fructose-Specific Memory And Catabolite Repression In Lactose Metabolism Bystreptococcus Mutans

Lactose is an abundant dietary carbohydrate metabolized by the dental pathogenStreptococcus mutans. Lactose metabolism presents both classic diauxic behaviors and long-term memory, where the bacteria can pause for >11 h before initiating growth on lactose. Here, we explored mechanisms contributing to unusual aspects of regulation of thelacoperon. The fructose-phosphate metabolites, F-1-P and F-6-P, could modulate the DNA-binding activities of the lactose repressor. Recombinant LacR proteins bound upstream oflacAand Gal-6-P induced the formation of different LacR-DNA complexes. Deletion oflacRresulted in strain-specific growth phenotypes on lactose, but also on a number of mono- and di-saccharides that involve the glucose-PTS or glucokinase in their catabolism. The phenotypes were consistent with the novel findings that loss of LacR altered glucose-PTS activity and expression of the gene for glucokinase. CcpA was also shown to affect lactose metabolismin vivoand to bind to thelacApromoter region in vitro. Collectively, our study reveals complex molecular circuits controlling lactose metabolism inS. mutans, where LacR and CcpA integrate cellular and environmental cues to regulate metabolism of a variety of carbohydrates that are critical to persistence and pathogenicity ofS. mutans.