{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T06:05:25Z","timestamp":1790057125875,"version":"4.0.1"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004761","name":"Natural Science Foundation of Hainan Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004761","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Backgroud<\/jats:title>\n                    <jats:p>\n                      Carbapenem-resistant\n                      <jats:italic>Acinetobacter baumannii<\/jats:italic>\n                      (CRAB) has become a predominant nosocomial pathogen worldwide, with biofilm formation and quorum sensing (QS) primarily responsible for its high antimicrobial tolerance and clinical refractory infections. Targeting bacterial virulence rather than conventional bactericidal strategies represents a promising alternative to combat multidrug-resistant CRAB.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this study, we isolated a N-acyl homoserine lactonase YtnP from mangrove rhizosphere-derived\n                      <jats:italic>Bacillus licheniformis<\/jats:italic>\n                      T2. We comprehensively biochemically characterized the YtnP and systematically validated its potent quorum-quenching, antibiofilm and anti-virulence activities against clinical CRAB strains both\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      YtnP is a 280-amino-acid metalloenzyme of approximately 30 kDa containing a conserved HXHXDH motif, exhibiting optimal activity at 37\u00b0C \u201345\u00b0C and pH 7.0\u20137.5. Distinct from classical lactonases, YtnP maintained high catalytic activity without exogenous Zn\n                      <jats:sup>2+<\/jats:sup>\n                      supplementation but was markedly inhibited by EDTA and excess Zn\n                      <jats:sup>2+<\/jats:sup>\n                      . Functional assays revealed that YtnP efficiently degraded the key QS signal 3-OH-C12-HSL with a degradation rate of 59.5% without affecting the planktonic growth of CRAB. YtnP significantly dismantled mature CRAB biofilms, reducing biofilm biomass by 55.56% and maximum thickness by 61.76%, and prominently downregulated the transcription of virulence-related outer membrane protein genes\n                      <jats:italic>ompA<\/jats:italic>\n                      and\n                      <jats:italic>csuA\/B<\/jats:italic>\n                      by nearly 50% and 52.6%, respectively. In the\n                      <jats:italic>Galleria mellonella<\/jats:italic>\n                      model, YtnP remarkably alleviated CRAB metabolite-induced lethality and increased the 36-h larval survival rate nearly sixfold.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Collectively, mangrove-derived YtnP acts as a potent quorum-quenching enzyme that suppresses CRAB biofilm formation and virulence in a non-bactericidal manner. This work highlights the potential of YtnP as a promising anti-virulence adjuvant candidate for the development of alternative therapeutic strategies against intractable CRAB infections.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1892272","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T05:41:07Z","timestamp":1790055667000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["YtnP lactonase from Bacillus licheniformis T2 mitigates virulence and biofilm formation in carbapenem-resistant Acinetobacter baumannii via quorum sensing quenching"],"prefix":"10.3389","volume":"17","author":[{"given":"Bin","family":"Liu","sequence":"first","affiliation":[{"name":"Key Laboratory of Emergency and Trauma of Ministry of Education, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital, Hainan Medical University","place":["Haikou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caihua","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Emergency and Trauma of Ministry of Education, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital, Hainan Medical University","place":["Haikou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizhen","family":"Zhu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Emergency and Trauma of Ministry of Education, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital, Hainan Medical University","place":["Haikou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengxia","family":"Zhu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Emergency and Trauma of Ministry of Education, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital, Hainan Medical University","place":["Haikou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jilai","family":"Yin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Emergency and Trauma of Ministry of Education, Department of Microbiology Laboratory, The First Affiliated Hospital, Hainan Medical University","place":["Haikou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Emergency and Trauma of Ministry of Education, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital, Hainan Medical University","place":["Haikou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1186\/s12879-025-10923-5","article-title":"Antimicrobial resistance pattern of Acinetobacter baumannii clinical isolate in Ethiopia. A systematic review and meta-analysis.","volume":"25","author":"Asmare","year":"2025","journal-title":"BMC Infect. Dis."},{"key":"B2","doi-asserted-by":"publisher","first-page":"106473","DOI":"10.1016\/j.micpath.2023.106473","article-title":"Anti-OmpA antibodies as potential inhibitors of Acinetobacter baumannii biofilm formation, adherence to, and proliferation in A549 human alveolar epithelial cells.","volume":"186","author":"Barati","year":"2024","journal-title":"Microb. Pathog."},{"key":"B3","doi-asserted-by":"publisher","first-page":"e00278-19","DOI":"10.1128\/IAI.00278-19","article-title":"Interference with Pseudomonas aeruginosa quorum sensing and virulence by the mycobacterial Pseudomonas Quinolone signal dioxygenase AqdC in combination with the N-Acylhomoserine lactone lactonase QsdA.","volume":"87","author":"Birmes","year":"2019","journal-title":"Infect. Immun."},{"key":"B4","doi-asserted-by":"publisher","first-page":"dlaf134","DOI":"10.1093\/jacamr\/dlaf134","article-title":"The global epidemiology of carbapenem-resistant Acinetobacter baumannii.","volume":"7","author":"Boutzoukas","year":"2025","journal-title":"JAC Antimicrob. Resist."},{"key":"B5","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1038\/s41579-022-00682-4","article-title":"Tolerance and resistance of microbial biofilms.","volume":"20","author":"Ciofu","year":"2022","journal-title":"Nat. Rev. Microbiol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"130421","DOI":"10.1016\/j.ijbiomac.2024.130421","article-title":"A novel thermostable YtnP lactonase from Stenotrophomonas maltophilia inhibits Pseudomonas aeruginosa virulence in vitro and in vivo.","volume":"264","author":"Curcic","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"906312","DOI":"10.3389\/fmicb.2022.906312","article-title":"Novel quorum quenching YtnP lactonase from Bacillus paralicheniformis reduces Pseudomonas aeruginosa virulence and increases antibiotic efficacy in vivo.","volume":"13","author":"Djokic","year":"2022","journal-title":"Front. Microbiol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"2664980","DOI":"10.1080\/21505594.2026.2664980","article-title":"Acinetobacter baumannii: Mechanisms of antibiotic resistance, quorum sensing regulation, and current therapeutic strategies.","volume":"17","author":"Fortaleza","year":"2026","journal-title":"Virulence"},{"key":"B9","doi-asserted-by":"publisher","first-page":"ftae009","DOI":"10.1093\/femspd\/ftae009","article-title":"Disrupting quorum sensing as a strategy to inhibit bacterial virulence in human, animal, and plant pathogens.","volume":"82","author":"Gonzales","year":"2024","journal-title":"Pathog. Dis."},{"key":"B10","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1099\/ijsem.0.002482","article-title":"Bacillus marinisedimentorum sp. nov., isolated from marine sediment.","volume":"68","author":"Guo","year":"2018","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"127032","DOI":"10.1016\/j.micres.2022.127032","article-title":"The role of quorum sensing, biofilm formation, and iron acquisition as key virulence mechanisms in Acinetobacter baumannii and the corresponding anti-virulence strategies.","volume":"260","author":"Law","year":"2022","journal-title":"Microbiol. Res."},{"key":"B12","doi-asserted-by":"publisher","first-page":"101310","DOI":"10.1016\/j.jpha.2025.101310","article-title":"Virulence arresting drug discovery by strategies targeting bacterial virulence: Mainly focusing on quorum-sensing interference and biofilm inhibition.","volume":"15","author":"Lu","year":"2025","journal-title":"J. Pharm. Anal."},{"key":"B13","doi-asserted-by":"publisher","first-page":"310","DOI":"10.3389\/fcimb.2018.00310","article-title":"Multiple quorum quenching enzymes are active in the nosocomial pathogen Acinetobacter baumannii ATCC17978.","volume":"8","author":"Mayer","year":"2018","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"126722","DOI":"10.1016\/j.micres.2021.126722","article-title":"An overview of Acinetobacter baumannii pathogenesis: Motility, adherence and biofilm formation.","volume":"247","author":"Mea","year":"2021","journal-title":"Microbiol. Res."},{"key":"B15","doi-asserted-by":"publisher","first-page":"782733","DOI":"10.3389\/fcimb.2021.782733","article-title":"Galleria mellonella as a suitable model of bacterial infection: Past. Present and Future.","volume":"11","author":"M\u00e9nard","year":"2021","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1601","DOI":"10.3389\/fmicb.2019.01601","article-title":"The mechanisms of disease caused by Acinetobacter baumannii.","volume":"10","author":"Morris","year":"2019","journal-title":"Front. Microbiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1186\/s12929-020-0617-7","article-title":"Outer membrane protein A (OmpA) as a potential therapeutic target for Acinetobacter baumannii infection.","volume":"27","author":"Nie","year":"2020","journal-title":"J. Biomed. Sci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1080\/20477724.2021.1916158","article-title":"Foodborne ESKAPE biofilms and antimicrobial resistance: Lessons learned from clinical isolates.","volume":"115","author":"Patil","year":"2021","journal-title":"Pathog Glob. Health"},{"key":"B19","doi-asserted-by":"publisher","first-page":"631","DOI":"10.3390\/antibiotics10060631","article-title":"Attenuation of Aeromonas hydrophila infection in Carassius auratus by YtnP, a N-acyl homoserine lactonase from Bacillus licheniformis T-1.","volume":"10","author":"Peng","year":"2021","journal-title":"Antibiotics"},{"key":"B20","doi-asserted-by":"publisher","first-page":"ftaa056","DOI":"10.1093\/femspd\/ftaa056","article-title":"Galleria mellonella as an infection model: An in-depth look at why it works and practical considerations for successful application.","volume":"78","author":"Pereira","year":"2020","journal-title":"Pathog. Dis."},{"key":"B21","doi-asserted-by":"publisher","first-page":"21521","DOI":"10.1038\/s41598-024-72740-1","article-title":"Impact of AbaI mutation on virulence, biofilm development, and antibiotic susceptibility in Acinetobacter baumannii.","volume":"14","author":"Pumirat","year":"2024","journal-title":"Sci. Rep."},{"key":"B22","doi-asserted-by":"publisher","first-page":"dlae052","DOI":"10.1093\/jacamr\/dlae052","article-title":"Antimicrobial resistance of clinical bacterial isolates in China: Current status and trends.","volume":"6","author":"Qin","year":"2024","journal-title":"JAC Antimicrob. Resist."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1007\/s42770-021-00624-x","article-title":"Microbial biofilm: Formation, architecture, antibiotic resistance, and control strategies.","volume":"52","author":"Rather","year":"2021","journal-title":"Braz. J. Microbiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1186\/s13007-022-00944-5","article-title":"Protocol: A simple method for biosensor visualization of bacterial quorum sensing and quorum quenching interaction on Medicago roots.","volume":"18","author":"Rosier","year":"2022","journal-title":"Plant Methods"},{"key":"B25","doi-asserted-by":"publisher","first-page":"829","DOI":"10.3390\/microorganisms13040829","article-title":"The multifaceted landscape of healthcare-associated infections caused by carbapenem-resistant Acinetobacter baumannii.","volume":"13","author":"Russo","year":"2025","journal-title":"Microorganisms"},{"key":"B26","doi-asserted-by":"publisher","first-page":"4273","DOI":"10.2147\/IDR.S276970","article-title":"Contribution of the AbaI\/AbaR quorum sensing system to resistance and virulence of Acinetobacter baumannii Clinical Strains.","volume":"13","author":"Tang","year":"2020","journal-title":"Infect. Drug Resist."},{"key":"B27","doi-asserted-by":"publisher","first-page":"16570","DOI":"10.3390\/ijms140816570","article-title":"Development of quorum-based anti-virulence therapeutics targeting Gram-negative bacterial pathogens.","volume":"14","author":"Tay","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"B28","doi-asserted-by":"publisher","first-page":"3398","DOI":"10.1099\/mic.0.2008\/019471-0","article-title":"Characterization of a two-component regulatory system from Acinetobacter baumannii that controls biofilm formation and cellular morphology.","volume":"154","author":"Tomaras","year":"2008","journal-title":"Microbiology"},{"key":"B29","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1080\/08927014.2023.2215693","article-title":"Targeting outer membrane protein A (OmpA) - inhibitory effect of 2\u2019-hydroxychalcone derivatives on Acinetobacter baumannii and Candida albicans dual-species biofilm formation.","volume":"39","author":"U\u0161jak","year":"2023","journal-title":"Biofouling"},{"key":"B30","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1007\/s00203-020-02061-0","article-title":"5-Hydroxymethylfurfural inhibits Acinetobacter baumannii biofilms: An in vitro study.","volume":"203","author":"Vijayakumar","year":"2021","journal-title":"Arch. Microbiol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1007\/s10126-014-9585-9","article-title":"Quorum-quenching activity of the AHL-lactonase from Bacillus licheniformis DAHB1 inhibits Vibrio biofilm formation in vitro and reduces shrimp intestinal colonisation and mortality.","volume":"16","author":"Vinoj","year":"2014","journal-title":"Mar. Biotechnol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1186\/s12866-022-02612-z","article-title":"Transcriptomic analysis reveals the regulatory role of quorum sensing in the Acinetobacter baumannii ATCC 19606 via RNA-seq.","volume":"22","author":"Xiong","year":"2022","journal-title":"BMC Microbiol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"116058","DOI":"10.1016\/j.lwt.2024.116058","article-title":"YtnP: One novel quorum quenching enzyme from Bacillus amyloliquefaciensW11 inhibits biofilms and spoilage of white radish by Serratia marcescens.","volume":"198","author":"Xu","year":"2024","journal-title":"LWT \u2013 Food Sci. Technol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"5749982","DOI":"10.1155\/ijm\/5749982","article-title":"Characterization and biofilm inhibition of multidrug-resistant Acinetobacter baumannii Isolates.","volume":"2024","author":"Yadav","year":"2024","journal-title":"Int. J. Microbiol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"558003","DOI":"10.3389\/fmicb.2021.558003","article-title":"Quorum sensing inhibition or quenching in Acinetobacter baumannii: The novel therapeutic strategies for new drug development.","volume":"12","author":"Zhong","year":"2021","journal-title":"Front. Microbiol."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1892272\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T05:41:08Z","timestamp":1790055668000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1892272\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,22]]},"references-count":35,"alternative-id":["10.3389\/fmicb.2026.1892272"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2026.1892272","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,22]]},"article-number":"1892272"}}