The interaction of sucrose and starch with bacterial glucosyltransferases and human salivary amylase may enhance the pathogenic potential of Streptococcus mutans within biofilms by influencing the structural organization of the extracellular matrix and modulating the expression of genes involved in exopolysaccharide synthesis and specific sugar transport and two-component systems.Oral diseases related to biofilms, such as dental caries, affect the majority of the world's population (27,34). Dental caries results from the interaction of specific bacteria and salivary constituents with dietary carbohydrates in the oral cavity; the appearance of biofilms on the tooth surface is the first clinical evidence of the diet-bacterium interaction. Sucrose is considered the "arch criminal" from the dietary standpoint because it is fermentable and also serves as a substrate for synthesis of extracellular polysaccharides (EPS) in dental biofilm (2, 28). Starches are an important source of fermentable carbohydrate and are usually consumed simultaneously with sucrose in modern societies. The combination of starch and sucrose is highly cariogenic in vivo (1, 10, 33) and may enhance the pathogenicity of biofilms in humans (30).Streptococcus mutans is a key contributor to the formation of cariogenic biofilms; this bacterium (i) synthesizes large amounts of extracellular glucans and fructans from sucrose using several glucosyltransferases (Gtfs) and a fructosyltransferase, (ii) adheres tenaciously to glucan-coated surfaces, and (iii) is highly acidogenic and acid tolerant, which are critical virulence properties in the pathogenesis of dental caries (2, 29, 31). Glucans provide specific binding sites for bacterial colonization on the tooth surface and bulk and structural integrity to the extracellular matrix; thus, they are essential for the formation and accumulation of dental biofilms (2). In addition, starches can be digested by ␣-amylases to maltose, maltodextrins, and other oligosaccharides, some of which can be acceptors during glucan synthesis by Gtfs (11,12,35). Starch hydrolysates produced by salivary ␣-amylases bound to saliva-coated hydroxyapatite (sHA) increased, in the presence of sucrose, the synthesis of structurally distinctive glucans by surface-adsorbed GtfB (35).Moreover, maltose and maltodextrins resulting from starch hydrolysis can be catabolized in acids by S. mutans (4). In this study, we investigated whether biochemical reactions involving interactions between specific host (␣-amylase) and bacterium-derived (Gtfs) enzymes and dietary carbohydrates (starch and sucrose) influence (i) the biochemical and structural properties of the EPS matrix and (ii) trigger specific adaptive responses by S. mutans at the transcriptional level, resulting in a biofilm with enhanced virulence.Biofilms of S. mutans UA159 (ϭ ATCC 700610) were formed using our amylase-active sHA disk model (18). Biofilms were grown in buffered tryptone yeast extract broth (pH 7.0) containing (i) 1% (wt/vol) starch (soluble starch [80% amylopectin a...