Swift-kinetics driven RSM optimized, biocompatible AgNPs inhibit uropathogenic biofilms via AHL interference: mechanistic insights from Ag8-SdiA in-silico docking

Swift-kinetics driven RSM optimized, biocompatible AgNPs inhibit uropathogenic biofilms via AHL interference: mechanistic insights from Ag8-SdiA in-silico docking | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Swift-kinetics driven RSM optimized, biocompatible AgNPs inhibit uropathogenic biofilms via AHL interference: mechanistic insights from Ag8-SdiA in-silico docking Saloni R. Mhavarkar, Sagar H. Barage, Kajal Jadhav, Shekhar B. Jadhav This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7963429/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 14 Apr, 2026 Read the published version in BioNanoScience → Version 1 posted 7 You are reading this latest preprint version Abstract Urinary Tract Infections remain a highly prevalent global health concern, with biofilm-forming, multidrug-resistant uropathogens such as Uropathogenic Escherichia coli ( UPEC ) and Enterobacter hormaechei posing significant therapeutic challenges. In this study, silver nanoparticles synthesized using Mussaenda philippica L. leaf extract were optimized through RSM, investigated for its rapid reaction kinetics, tested for application in quorum quenching and hence biofilm disruption against two uropathogens - UPEC and E. hormaechei . Mechanistic insights are gained by molecular docking of Ag8 nanocluster with SdiA receptor of AI-1 signals. Green synthesis was optimized using RSM, achieving high nanoparticles yield and activity under optimal conditions (pH 9, 45 °C, 1.4 mM AgNO₃, 1.125% extract). It is a pseudo-first-order behavior (k′ = 0.4463 min⁻¹, R² = 0.94) with a half-life of 1.55 min, indicating rapid, chemically driven Mp-AgNPs formation without lag phase. Long-term colloidal stability was observed, with unaltered SPR peaks over two months, attributed to effective phytochemical capping. Antibiofilm activity was evaluated using qualitative and quantitative assays. Mp-AgNPs inhibited biofilms by 69% in UPEC and 67.78% in E. hormaechei , and reduced EPS. Mp-AgNPs also suppressed AHLs production and cell surface hydrophobicity. Mechanistic investigation from molecular docking simulation revealed that Ag8 cluster bind within the hydrophobic cavity of SdiA regulators in both uropathogens via metal-acceptor co-ordination. This docking insights suggests that Ag8 interaction may disrupt SdiA function, providing a mechanistic basis for AgNPs mediated quorum sensing interference and biofilm inhibition. Finally, excellent biocompatibility with HaCaT cells represent Mp-AgNPs as a promising green nanotechnology-based approach to combat AMR/MDR in uropathogens. Biofilm Enterobacter hormaechei Molecular docking Quorum sensing SdiA Silver nanoparticles Urinary Tract Infections Full Text Additional Declarations No competing interests reported. Supplementary Files SupplementaryDataWJMB.docx Cite Share Download PDF Status: Published Journal Publication published 14 Apr, 2026 Read the published version in BioNanoScience → Version 1 posted Editorial decision: Revision requested 27 Jan, 2026 Reviews received at journal 30 Dec, 2025 Reviewers agreed at journal 24 Nov, 2025 Reviewers invited by journal 24 Nov, 2025 Editor assigned by journal 05 Nov, 2025 Submission checks completed at journal 04 Nov, 2025 First submitted to journal 27 Oct, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7963429","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":537887340,"identity":"819ccd89-ed4a-42f4-8fd0-3e7894df6987","order_by":0,"name":"Saloni R. 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In this study, silver nanoparticles synthesized using \u003cem\u003eMussaenda philippica\u003c/em\u003e L. leaf extract were optimized through RSM, investigated for its rapid reaction kinetics, tested for application in quorum quenching and hence biofilm disruption against two uropathogens - \u003cem\u003eUPEC\u003c/em\u003e and \u003cem\u003eE. hormaechei\u003c/em\u003e. Mechanistic insights are gained by molecular docking of Ag8 nanocluster with SdiA receptor of AI-1 signals. Green synthesis was optimized using RSM, achieving high nanoparticles yield and activity under optimal conditions (pH 9, 45 °C, 1.4 mM AgNO₃, 1.125% extract). It is a pseudo-first-order behavior (k′ = 0.4463 min⁻¹, \u003cem\u003eR²\u003c/em\u003e = 0.94) with a half-life of 1.55 min, indicating rapid, chemically driven Mp-AgNPs formation without lag phase. Long-term colloidal stability was observed, with unaltered SPR peaks over two months, attributed to effective phytochemical capping. Antibiofilm activity was evaluated using qualitative and quantitative assays. Mp-AgNPs inhibited biofilms by 69% in \u003cem\u003eUPEC\u003c/em\u003e and 67.78% in \u003cem\u003eE. hormaechei\u003c/em\u003e, and reduced EPS. Mp-AgNPs also suppressed AHLs production and cell surface hydrophobicity. Mechanistic investigation from molecular docking simulation revealed that Ag8 cluster bind within the hydrophobic cavity of SdiA regulators in both uropathogens via metal-acceptor co-ordination. This docking insights suggests that Ag8 interaction may disrupt SdiA function, providing a mechanistic basis for AgNPs mediated quorum sensing interference and biofilm inhibition. Finally, excellent biocompatibility with HaCaT cells represent Mp-AgNPs as a promising green nanotechnology-based approach to combat AMR/MDR in uropathogens.\u003c/p\u003e","manuscriptTitle":"Swift-kinetics driven RSM optimized, biocompatible AgNPs inhibit uropathogenic biofilms via AHL interference: mechanistic insights from Ag8-SdiA in-silico docking","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-03 03:37:13","doi":"10.21203/rs.3.rs-7963429/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-01-28T02:40:51+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-30T06:21:21+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"108062266649779375583508331476651199390","date":"2025-11-24T12:04:17+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-24T09:08:50+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-05T07:26:50+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-11-04T13:08:13+00:00","index":"","fulltext":""},{"type":"submitted","content":"BioNanoScience","date":"2025-10-27T19:13:56+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bionanoscience","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bnsc","sideBox":"Learn more about [BioNanoScience](http://link.springer.com/journal/12668)","snPcode":"12668","submissionUrl":"https://submission.nature.com/new-submission/12668/3","title":"BioNanoScience","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"fc437f7f-2a6c-4035-bada-46d8f34e5e29","owner":[],"postedDate":"November 3rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-04-20T16:03:08+00:00","versionOfRecord":{"articleIdentity":"rs-7963429","link":"https://doi.org/10.1007/s12668-026-02526-4","journal":{"identity":"bionanoscience","isVorOnly":false,"title":"BioNanoScience"},"publishedOn":"2026-04-14 15:59:48","publishedOnDateReadable":"April 14th, 2026"},"versionCreatedAt":"2025-11-03 03:37:13","video":"","vorDoi":"10.1007/s12668-026-02526-4","vorDoiUrl":"https://doi.org/10.1007/s12668-026-02526-4","workflowStages":[]},"version":"v1","identity":"rs-7963429","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7963429","identity":"rs-7963429","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}