A Drug Repositioning Approach Reveals that Streptococcus mutans Is Susceptible to a Diverse Range of Established Antimicrobials and Nonantibiotics

Antimicrob Agents Chemother. 2017 Dec 21;62(1):e01674-17. doi: 10.1128/AAC.01674-17. Print 2018 Jan.

Abstract

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 (Selleck Chemical, Houston, TX) 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 preexisting biofilms, 84 exhibited biofilm inhibition and killing activity, and 12 had no activity against biofilms. The activities 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.

Keywords: Streptococcus mutans; antibiotics; dental caries; high-throughput screen.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Deterrents / pharmacology
  • Anti-Bacterial Agents / pharmacology*
  • Antifungal Agents / pharmacology
  • Antineoplastic Agents / pharmacology
  • Biofilms / drug effects
  • Dental Caries / microbiology
  • Dental Plaque / microbiology
  • Disulfiram / pharmacology
  • Drug Repositioning*
  • High-Throughput Screening Assays
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Ion Channels / drug effects
  • Microbial Sensitivity Tests
  • Streptococcus mutans / drug effects*

Substances

  • Alcohol Deterrents
  • Anti-Bacterial Agents
  • Antifungal Agents
  • Antineoplastic Agents
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Ion Channels
  • Disulfiram