A drug repositioning approach reveals Streptococcus mutans is susceptible to a diverse range of established antimicrobials and non-antibiotics [PublishAheadOfPrint]

Streptococcus mutans is the primary causative agent of dental caries and contributes to the multispecies biofilm known as dental plaque. An adenylate kinase-based assay was optimized for S. mutans to detect cell lysis when exposed to the Selleck library of 853 FDA-approved drugs, in, to our knowledge, the first high-throughput drug screen in S. mutans. We found 126 drugs with activity against S. mutans planktonic cultures and they were classified into six categories: antibacterials (61), antineoplastics (23), ion channel effectors (9), other antimicrobials (7), antifungals (6), and other (20). These drugs were also tested for activity against S. mutans biofilm cultures, and 24 compounds were found to inhibit biofilm formation, 6 killed pre-existing biofilms, 84 exhibited biofilm inhibition and killing activity, and 12 had no activity against biofilms. The activity of 9 selected compounds that exhibited antimicrobial activity were further characterized for their activity against S. mutans planktonic and biofilm cultures. Together, our results suggest that S. mutans exhibits a susceptibility profile to a diverse array of established and novel antibacterials.

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