Inhibition of Streptococcus mutans adhesion and biofilm formation with small-molecule inhibitors of sortase A from Juniperus chinensis

Background Streptococcus mutans, an important Gram-positive pathogen in dental caries, uses sortase A (SrtA) to anchor surface proteins to the bacterial cell wall, thereby promoting biofilm formation and attachment to the tooth surface. Design Based on activity-guided separation, inhibitors of S. mutans SrtA were isolated from Juniperus chinensis and identified through combined spectroscopic analysis. Further effects of isolated SrtA inhibitor on S. mutans were evaluated on bacterial aggregation, adherence and biofilm formation. Results Six compounds (1-6) were isolated from the dried heartwood of J. chinensis. A novel compound designated 3',3"-dihydroxy-(-)-matairesinol (1) was identified, which exhibited potent inhibitory activity toward S. mutans SrtA (IC50 = 16.1 mu M) without affecting microbial viability (minimum inhibitory concentration > 300 mu M). The results of subsequent bioassays using compound 1 indicated that this compound inhibits S. mutans aggregation, adhesion and biofilm formation on solid surfaces by inhibiting SrtA activity. The onset and magnitude of inhibition of adherence and biofilm formation in S. mutans treated with compound 1 at 4x the SrtA IC50 are comparable to the behaviors of the untreated srtA-deletion mutant. Conclusion Our findings suggest that small-molecule inhibitors of S. mutans SrtA may be useful for the prevention of dental plaque and treatment of dental microbial diseases.N