{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T22:47:52Z","timestamp":1788821272013,"version":"build-2803163510"},"reference-count":55,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2025,11,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Aggregatibacter actinomycetemcomitans<\/jats:italic>\n                      is a key pathogen\n                        implicated in periodontitis. The bacterium in biofilms exhibits significant\n                        resistance to antimicrobial agents and host immune responses compared to its\n                        planktonic form, posing a major challenge for periodontal therapy. Recently,\n                        D-histidine has emerged as a promising anti-biofilm agent against\n                      <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                      infections. However, its\n                        potential application in the oral field remains unexplored. This study\n                        investigated the anti-biofilm effect of D-histidine on\n                      <jats:italic toggle=\"yes\">A.\n                            actinomycetemcomitans<\/jats:italic>\n                      and examined its influence on the\n                        expression of virulence factor genes to elucidate possible underlying\n                        mechanisms. Our results demonstrated that D-histidine inhibited biofilm\n                        formation and disrupted established biofilms in a concentration-dependent\n                        manner, without affecting bacterial growth. Furthermore, D-histidine\n                        downregulated the expression of virulence factors by inhibiting quorum\n                        sensing (QS)-related genes. Notably, combining D-histidine with antibiotics,\n                        such as amoxicillin, minocycline, and metronidazole, synergistically\n                        enhanced biofilm eradication and enabled the use of lower antibiotic\n                        dosages. These findings support the further evaluation of D-histidine as a\n                        potential anti-biofilm agent in the treatment of periodontitis.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        The increasing prevalence of antibiotic-resistant\n                        <jats:italic toggle=\"yes\">A.\n                                actinomycetemcomitans<\/jats:italic>\n                        biofilms posed a significant\n                            challenge in periodontitis management. This study demonstrated that\n                            D-histidine effectively targeted\n                        <jats:italic toggle=\"yes\">A.\n                                actinomycetemcomitans<\/jats:italic>\n                        biofilms by disrupting structural\n                            integrity and suppressing virulence gene expression, without exerting\n                            bactericidal effects that could promote resistance development. Notably,\n                            D-histidine showed potent synergy with minocycline, significantly\n                            enhancing biofilm eradication while potentially enabling reduced\n                            antibiotic dosages. These findings established D-histidine as a\n                            promising adjunctive therapeutic agent, addressing the urgent need for\n                            novel approaches to overcome biofilm-associated antibiotic tolerance in\n                            periodontal treatment.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.01216-25","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T13:02:18Z","timestamp":1759150938000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["D-histidine exhibited anti-biofilm activity against\n                    <i>Aggregatibacter actinomycetemcomitans<\/i>"],"prefix":"10.1128","volume":"13","author":[{"given":"Wenwen","family":"Shan","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03xb04968","id-type":"ROR","asserted-by":"publisher"}],"name":"Stomatological Hospital and College, Key Lab. of Oral Diseases Research of Anhui Province, Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fen","family":"Du","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03xb04968","id-type":"ROR","asserted-by":"publisher"}],"name":"Stomatological Hospital and College, Key Lab. of Oral Diseases Research of Anhui Province, Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haichuan","family":"Zhang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03xb04968","id-type":"ROR","asserted-by":"publisher"}],"name":"Stomatological Hospital and College, 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