With the rise of antimicrobial resistance, scientists are searching for new methods to eradicate bacterial infections. Bacterial pathogenicity is commonly targeted to prevent emerging resistance development by decreasing the selection stresses that are present with traditional antibiotics. A key contributor to pathogenicity are biofilms, communities of cells that create an economic burden for several industries and are common in many disease states in human health. Streptococcus mutans is a Gram-positive microorganism that is used for the study of biofilm pathogenicity and is the causative agent in the formation of dental caries, the most prevalent childhood disease. Our research program has a continued interest in developing novel small molecule probes that specifically target S. mutans biofilm growth. Carolacton (–)-1 is a myxobacterium natural product that was identified to induce cell defects in S. mutans biofilms. Unfortunately, carolacton’s utility is limited due to the complexity of the structure and the inability of performing quick, prolific biological assays since cells must be imaged to determine effect. Herein, the development and synthesis of a simplified natural product, (+)-2, will be disclosed. This compound enables further characterization of biological activity since it exhibits a quantifiable growth inhibition in biofilm cultures. Using this simplified chemical structure we have gathered evidence that our compounds are acting via an acid tolerance mechanism and have identified a putative biofilm target.

Synthesis of a carolacton tool compound enables identification of a unique biofilm target in Streptococcus mutans

2019 Fall National Meeting

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