{Reference Type}: Journal Article {Title}: Subpopulation behaviors in lactose metabolism by Streptococcus mutans. {Author}: Zeng L;Burne RA; {Journal}: Mol Microbiol {Volume}: 115 {Issue}: 1 {Year}: 01 2021 {Factor}: 3.979 {DOI}: 10.1111/mmi.14596 {Abstract}: When Streptococcus mutans is transferred from a preferred carbohydrate (glucose or fructose) to lactose, initiation of growth can take several hours, and substantial amounts of glucose are released during growth. Here, S. mutans strains UA159 and GS-5 were examined for stochastic behaviors in transcription of the lac operon. Using a gfp reporter fusion, we demonstrated that induction of the lac operon occurs in only a fraction of the population, with prior exposure to carbohydrate source and strain influencing the magniture of the sub-population response. Lower glucokinase activity in GS-5 was associated with release of substantially more glucose than UA159 and significantly lower lac expression. Mutants unable to use lactose grew on lactose as the sole carbohydrate when strains with an intact lac operon were also present in the cultures, indicative of the potential for population cheating. Utilizing a set of engineered obligate cheating and non-cheating strains, we confirmed that cheating can sustain a heterogeneous population. Futher, obligate cheaters of GS-5 competed well with the non-cheaters and showed a high degree of competitive fitness in a human-derived consortium biofilm model. The results show that bet-hedging behaviors in carbohydrate metabolism may substantially influence the composition and pathogenic potential of oral biofilms.