{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T04:35:30Z","timestamp":1772598930814,"version":"3.50.1"},"posted":{"date-parts":[[2024,1,18]]},"group-title":"Microbiology","reference-count":51,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,1,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Microorganisms resist fluoride toxicity using fluoride export proteins from one of several different molecular families. Cariogenic species\n                  <jats:italic>Streptococcus mutans<\/jats:italic>\n                  and\n                  <jats:italic>Candida albicans<\/jats:italic>\n                  extrude intracellular fluoride using a CLC\n                  <jats:sup>F<\/jats:sup>\n                  F\n                  <jats:sup>\u2212<\/jats:sup>\n                  \/H\n                  <jats:sup>+<\/jats:sup>\n                  antiporter and FEX fluoride channel, respectively, whereas commensal eubacteria, such as\n                  <jats:italic>Streptococcus gordonii,<\/jats:italic>\n                  export fluoride using a Fluc fluoride channel. In this work, we examine how genetic knockout of fluoride export impacts pathogen fitness in single-species and three-species dental biofilm models. For biofilms generated using\n                  <jats:italic>S. mutans<\/jats:italic>\n                  with genetic knockout of the CLC\n                  <jats:sup>F<\/jats:sup>\n                  transporter, exposure to low fluoride concentrations decreased\n                  <jats:italic>S. mutans<\/jats:italic>\n                  counts, synergistically reduced the populations of\n                  <jats:italic>C. albicans<\/jats:italic>\n                  , increased the relative proportion of commensal\n                  <jats:italic>S. gordonii<\/jats:italic>\n                  , and reduced properties associated with biofilm pathogenicity, including acid production and hydroxyapatite dissolution. Biofilms prepared with\n                  <jats:italic>C. albicans<\/jats:italic>\n                  with genetic knockout of the FEX channel also exhibited reduced fitness in the presence of fluoride, but to a lesser degree. Imaging studies indicate that\n                  <jats:italic>S. mutans<\/jats:italic>\n                  is highly sensitive to fluoride, with the knockout strain undergoing complete lysis when exposed to low fluoride for a moderate amount of time, and biochemical purification the\n                  <jats:italic>S. mutans<\/jats:italic>\n                  CLC\n                  <jats:sup>F<\/jats:sup>\n                  transporter and functional reconstitution establishes that the functional protein is a dimer encoded by a single gene. Together, these findings suggest that fluoride export by oral pathogens can be targeted by specific inhibitors to restore biofilm symbiosis in dental biofilms, and that\n                  <jats:italic>S. mutans<\/jats:italic>\n                  is especially susceptible to fluoride toxicity.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Importance<\/jats:title>\n                  <jats:p>\n                    Dental caries is a globally prevalent condition that occurs when pathogenic species, including\n                    <jats:italic>Streptococcus mutans<\/jats:italic>\n                    and\n                    <jats:italic>Candida albicans<\/jats:italic>\n                    , outcompete beneficial species, such as\n                    <jats:italic>Streptococcus gordonii,<\/jats:italic>\n                    in the dental biofilm. Fluoride is routinely used in oral hygiene to prevent dental caries. Fluoride also has antimicrobial properties, although most microbes possess fluoride exporters to resist its toxicity. This work shows that sensitization of cariogenic species\n                    <jats:italic>Streptococcus mutans<\/jats:italic>\n                    and\n                    <jats:italic>Candida albicans<\/jats:italic>\n                    to fluoride by genetic knockout of fluoride exporters alters the microbial composition and pathogenic properties of dental biofilms. These results suggest that the development of drugs that inhibit fluoride exporters could potentiate the anticaries effect of fluoride in over-the-counter products like toothpastes and mouth rinses. This is a novel strategy to treat dental caries.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.01.18.576223","type":"posted-content","created":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T19:15:13Z","timestamp":1705605313000},"source":"Crossref","is-referenced-by-count":1,"title":["Fluoride export is required for competitive fitness of pathogenic microorganisms in dental biofilm models"],"prefix":"10.64898","author":[{"given":"Aditya","family":"Banerjee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chia-Yu","family":"Kang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minjun","family":"An","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B. 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