AUTHOR=Zhang Meng , Yu Wenqian , Zhou Shujing , Zhang Bing , Lo Edward Chin Man , Xu Xin , Zhang Dongjiao 

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

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.647611

DOI=10.3389/fmicb.2021.647611

ISSN=1664-302X

ABSTRACT=<sec><title>Background</title><p>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.</p></sec><sec><title>Objectives</title><p>To assess the <italic>in vitro</italic> antibacterial activities of bedaquiline against oral pathogens in acidic milieus.</p></sec><sec><title>Methods</title><p><italic>Streptococcus mutans</italic>, <italic>Streptococcus sanguinis</italic>, and <italic>Streptococcus salivarius</italic> were used to prepare the mono-/multiple suspension and biofilm. The MIC and IC<sub>50</sub> of bedaquiline against <italic>S. mutans</italic> 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 <italic>S. mutans</italic> biofilm; (iii) the cytotoxicity effects; and (iv) the activity on H<sup>+</sup>-ATPase enzyme of <italic>S. mutans</italic>.</p></sec><sec><title>Results</title><p>In pH 5 BHI, 2.5 mg/L (IC<sub>50</sub>) and 4 mg/L (MIC) of bedaquiline inhibited the proliferation and biofilm generation of <italic>S. mutans</italic> 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 (&gt;56 mg/L) against H<sup>+</sup>-ATPase enzyme in <italic>S. mutans</italic> and its non-toxic effect (&lt;10 mg/L) on periodontal ligament stem cells were also confirmed.</p></sec><sec><title>Conclusion</title><p>Bedaquiline is efficient in inhibiting the proliferation and biofilm generation of <italic>S. mutans</italic> 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.</p></sec>