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This matrix provides structural stability, retains nutrients and offers defence against unfavourable environments and antibiotics. Multi-layered molecular mechanisms controlled by quorum-sensing networks are involved in the transition from the planktonic stage to a mature biofilm. Surface attachment, maturation and dispersion are coordinated by these mechanisms, which also provide communication between different species. Biofilm development poses a significant challenge to implants in nosocomial settings and is considered a major threat in the global health care sector and industries, leading to persistent infection. In addition to assessing current biofilm management techniques such as quorum quenching agents, enzymatic matrix disruptions, antimicrobial peptides, nanoparticles and metal complex-based interventions, this review highlights the major regulatory components and molecular mechanisms causing biofilm formation. It also emphasises the necessity to combat biofilm-associated tolerance by highlighting the increasing significance of computational approaches in drug discovery and development of next-generation anti-biofilm therapeutics.<\/jats:p>","DOI":"10.3389\/fcimb.2026.1826282","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T05:37:35Z","timestamp":1777354655000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Biofilm-associated antibiotic tolerance in the era of multidrug resistance: quorum-sensing mechanisms and emerging therapeutic strategies"],"prefix":"10.3389","volume":"16","author":[{"given":"Tarunkarthick","family":"Subramani","sequence":"first","affiliation":[{"name":"Department of Biotechnology, School of Biosciences and Technology, Vellore Institute of Technology (VIT)","place":["Vellore, Tamil Nadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth Annie","family":"George","sequence":"additional","affiliation":[{"name":"Department of Bio-Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT)","place":["Vellore, Tamil Nadu, India"]},{"name":"Medical and Biological Computing Laboratory, School of Biosciences and Technology, Vellore Institute of Technology (VIT)","place":["Vellore, Tamil Nadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akash Eldhose","family":"Saju","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, School of Biosciences and Technology, Vellore Institute of Technology (VIT)","place":["Vellore, Tamil Nadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muralikrishnan","family":"E.","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, School of Biosciences and Technology, Vellore Institute of Technology (VIT)","place":["Vellore, Tamil Nadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranit","family":"De","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, School of Biosciences and Technology, Vellore Institute of Technology (VIT)","place":["Vellore, Tamil Nadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddharth A.","family":"K.","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, School of Biosciences and Technology, Vellore Institute of Technology (VIT)","place":["Vellore, Tamil Nadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudha","family":"Ramaiah","sequence":"additional","affiliation":[{"name":"Department of Bio-Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT)","place":["Vellore, Tamil Nadu, India"]},{"name":"Medical and Biological Computing Laboratory, School of Biosciences and Technology, Vellore Institute of Technology (VIT)","place":["Vellore, Tamil Nadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anand","family":"Anbarasu","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, School of Biosciences and Technology, Vellore Institute of Technology (VIT)","place":["Vellore, Tamil Nadu, India"]},{"name":"Medical and Biological Computing Laboratory, School of Biosciences and Technology, Vellore Institute of Technology (VIT)","place":["Vellore, Tamil Nadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1186\/s12866-024-03370-w","article-title":"Sorbate metal complexes as newer antibacterial, antibiofilm, and anticancer compounds","volume":"24","author":"Abousaty","year":"2024","journal-title":"BMC Microbiol."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imu.2022.100880","article-title":"Molecular modeling in drug discovery","volume":"29","author":"Adelusi","year":"2022","journal-title":"Inform. 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