1. Academic Validation
  2. In vitro Antibacterial Activity of an FDA-Approved H+-ATPase Inhibitor, Bedaquiline, Against Streptococcus mutans in Acidic Milieus

In vitro Antibacterial Activity of an FDA-Approved H+-ATPase Inhibitor, Bedaquiline, Against Streptococcus mutans in Acidic Milieus

  • Front Microbiol. 2021 Feb 25;12:647611. doi: 10.3389/fmicb.2021.647611.
Meng Zhang 1 2 Wenqian Yu 1 Shujing Zhou 3 Bing Zhang 1 Edward Chin Man Lo 2 Xin Xu 1 Dongjiao Zhang 1
Affiliations

Affiliations

  • 1 Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • 2 Faculty of Dentistry, University of Hong Kong, Sai Ying Pun, Hong Kong.
  • 3 Department of Stomatology, Maternal and Child Health Hospital of Liaocheng City, Liaocheng, China.
Abstract

Background: Dental caries is an acid-related disease. Current anti-caries agents mainly focus on the bacteriostatic effect in a neutral environment and do not target acid-resistant Microorganisms related to caries in acidic milieus.

Objectives: To assess the in vitro Antibacterial activities of bedaquiline against oral pathogens in acidic milieus.

Methods: Streptococcus mutans, Streptococcus sanguinis, and Streptococcus salivarius were used to prepare the mono-/multiple suspension and biofilm. The MIC and IC50 of bedaquiline against S. mutans were determined by the broth microdilution method. Bedaquiline was compared regarding (i) the inhibitory activity in pH 4-7 and at different time points against planktonic and biofilm; (ii) the effect on the production of lactic acid, extracellular polysaccharide, and pH of S. mutans biofilm; (iii) the cytotoxicity effects; and (iv) the activity on H+-ATPase Enzyme of S. mutans.

Results: In pH 5 BHI, 2.5 mg/L (IC50) and 4 mg/L (MIC) of bedaquiline inhibited the proliferation and biofilm generation of S. mutans and Mix in a dose-dependent and time-dependent manner, but it was invalid in a neutral environment. The lactic acid production, polysaccharide production, and pH drop range reduced with the incorporation of bedaquiline in a pH 5 environment. Its inhibitory effect (>56 mg/L) against H+-ATPase Enzyme in S. mutans and its non-toxic effect (<10 mg/L) on periodontal ligament stem cells were also confirmed.

Conclusion: Bedaquiline is efficient in inhibiting the proliferation and biofilm generation of S. mutans and other oral pathogens in an acidic environment. Its high targeting property and non-cytotoxicity also promote its clinical application potential in preventing caries. Further investigation of its specific action sites and drug modification are warranted.

Keywords

Streptococcus mutans; acid resistance bacteria; acidic environment; antibacteria activity; caries.

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