{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,30]],"date-time":"2025-08-30T16:50:48Z","timestamp":1756572648272,"version":"3.41.2"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T00:00:00Z","timestamp":1614211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013158","name":"Tai\u2019shan Scholar Engineering Construction Fund of Shandong Province of China","doi-asserted-by":"publisher","award":["TS201511106"],"award-info":[{"award-number":["TS201511106"]}],"id":[{"id":"10.13039\/501100013158","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009108","name":"Shandong University","doi-asserted-by":"publisher","award":["2018GN024"],"award-info":[{"award-number":["2018GN024"]}],"id":[{"id":"10.13039\/100009108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats: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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To assess the<jats:italic>in vitro<\/jats:italic>antibacterial activities of bedaquiline against oral pathogens in acidic milieus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:italic>Streptococcus mutans<\/jats:italic>,<jats:italic>Streptococcus sanguinis<\/jats:italic>, and<jats:italic>Streptococcus salivarius<\/jats:italic>were used to prepare the mono-\/multiple suspension and biofilm. The MIC and IC<jats:sub>50<\/jats:sub>of bedaquiline against<jats:italic>S. mutans<\/jats:italic>were determined by the broth microdilution method. Bedaquiline was compared regarding (i) the inhibitory activity in pH 4\u20137 and at different time points against planktonic and biofilm; (ii) the effect on the production of lactic acid, extracellular polysaccharide, and pH of<jats:italic>S. mutans<\/jats:italic>biofilm; (iii) the cytotoxicity effects; and (iv) the activity on H<jats:sup>+<\/jats:sup>-ATPase enzyme of<jats:italic>S. mutans<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In pH 5 BHI, 2.5 mg\/L (IC<jats:sub>50<\/jats:sub>) and 4 mg\/L (MIC) of bedaquiline inhibited the proliferation and biofilm generation of<jats:italic>S. mutans<\/jats: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 (&amp;gt;56 mg\/L) against H<jats:sup>+<\/jats:sup>-ATPase enzyme in<jats:italic>S. mutans<\/jats:italic>and its non-toxic effect (&amp;lt;10 mg\/L) on periodontal ligament stem cells were also confirmed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Bedaquiline is efficient in inhibiting the proliferation and biofilm generation of<jats:italic>S. mutans<\/jats: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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2021.647611","type":"journal-article","created":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T09:27:33Z","timestamp":1614245253000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["In vitro Antibacterial Activity of an FDA-Approved H+-ATPase Inhibitor, Bedaquiline, Against Streptococcus mutans in Acidic Milieus"],"prefix":"10.3389","volume":"12","author":[{"given":"Meng","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenqian","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shujing","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward Chin Man","family":"Lo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongjiao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1038\/s41586-018-0003-8","article-title":"Crystal structures of the gastric proton pump.","volume":"556","author":"Abe","year":"2018","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1126\/science.1106753","article-title":"A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis.","volume":"307","author":"Andries","year":"2005","journal-title":"Science"},{"key":"B3","doi-asserted-by":"publisher","first-page":"4869","DOI":"10.1021\/acsnano.9b02816","article-title":"Nanoparticles for oral biofilm treatments.","volume":"13","author":"Benoit","year":"2019","journal-title":"ACS Nano."},{"key":"B4","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.tim.2017.09.008","article-title":"Oral biofilms: pathogens, matrix, and polymicrobial interactions in microenvironments.","volume":"26","author":"Bowen","year":"2018","journal-title":"Trends Microbiol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.dental.2019.12.001","article-title":"Effects of S. mutans gene-modification and antibacterial monomer dimethylaminohexadecyl methacrylate on biofilm growth and acid production.","volume":"36","author":"Chen","year":"2020","journal-title":"Dent. 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