SMALL MOLECULE MEDIATED DISPERSION OF STREPTOCOCCUS MUTANS BIOFILMS BY A NEW MECHANISM
Stephanie Garcia1, Meghan Blackledge2, Christian Melander2, Hui Wu1.
1University of Alabama at Birmingham, Birmingham, AL, 2North Carolina State University, Raleigh, NC.
Dental caries is a costly disease characterized by the demineralization of the enamel and otherwise known as tooth decay. The etiologic causative agent of dental caries is Streptococcus mutans. S. mutans can use sugar to form hardy biofilms on the tooth surface and to rapidly produce lactic acid, which degrades enamel. In this study, we identify a novel small molecule capable of selectively dispersing S. mutans biofilms and elucidate its mode(s) of action. In order to develop a therapeutic agent that is species specific for S. mutans, we constructed a diverse library of small molecules based on the structural motifs of a natural product with antibiofilm and antibacterial properties. Small molecules were identified with a biofilm dispersion assay and characterized. We identified 3F1 as a novel small molecule that selectively disperses S. mutans biofilms. While 3F1 dispersed approximately half of S. mutans biofilms, it did not disperse biofilms formed by the commensal species Streptococcus sanguinis and Streptococcus gordonii. Addition of copper negated the effect of 3F1 and a copper chaperone (CopZ) mutant partially resisted dispersion by 3F1. Our data suggest 3F1 induces the dispersal of S. mutans biofilms by interacting with a unique copper-binding protein that plays a role in biofilm stabilization and maturation. Identification of the specific target of 3F1 is ongoing and will help determine the mechanism for 3F1 dispersal. The mechanism of 3F1 could lead to the discovery of a therapeutic target for the prevention or treatment of dental caries while maintaining the commensal populations.