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- Title
In vitro Antibacterial Activity of an FDA-Approved H<sup>+</sup>-ATPase Inhibitor, Bedaquiline, Against Streptococcus mutans in Acidic Milieus.
- Authors
Zhang, Meng; Yu, Wenqian; Zhou, Shujing; Zhang, Bing; Lo, Edward Chin Man; Xu, Xin; Zhang, Dongjiao
- 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.
- Subjects
STREPTOCOCCUS sanguis; PERIODONTAL ligament; LACTIC acid; DENTAL caries; STREPTOCOCCUS mutans; STEM cells
- Publication
Frontiers in Microbiology, 2021, Vol 11, pN.PAG
- ISSN
1664-302X
- Publication type
Article
- DOI
10.3389/fmicb.2021.647611