Simvastatin and Lovastatin inhibit Bacillus subtilis biofilm formation by interfering with the aggregation and amyloid formation of the TasA(28-261) –TapA(33-253) complex.

Simvastatin and Lovastatin inhibit Bacillus subtilis biofilm formation by interfering with the aggregation and amyloid formation of the TasA(28-261) –TapA(33-253) complex. | 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 Simvastatin and Lovastatin inhibit Bacillus subtilis biofilm formation by interfering with the aggregation and amyloid formation of the TasA (28-261) –TapA (33-253) complex. Nidhi Verma, Mamta Bajia, Abhishek Kumar Yadav, Chhavi Chaudhary, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4499575/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Statins have been reported for diverse pleiotropic activities, including antimicrobial and antibiofilm. However, due to the limited understanding of their mode of action, none of the statins have gained approval for antimicrobial or antibiofilm applications. In a recent drug-repurposing study, we observed that two statins (i.e., Simvastatin and Lovastatin) interact stably with TasA (28-261) , the principal extracellular matrix protein of Bacillus subtilis , leading to the inhibition of biofilm formation. Nevertheless, the precise mechanism underlying the biofilm inhibition remained elusive. In the present study, we examined the impact of these statins on the physiological activity of TasA (28-261 , specifically its interaction with TapA (33-253) and aggregation into the amyloid-like structure using purified recombinant TasA (28-261) and TapA (33-253) in amyloid detection specific in vitro assays (i.e., CR binding & ThT staining assays). Results revealed that both statins interfered with amyloid formation by TasA (28-261) -TapA (33-253) complex, while neither statin inhibited amyloid formation by lysozyme, a model amyloid-forming protein. Moreover, neither statin significantly altered the expressions of terminal regulatory genes (viz., sinR , sinI ) and effector genes (viz., tasA , tapA , and bslA ) involved in biofilm formation by B. subtilis. These findings divulge that Simvastatin and Lovastatin inhibit biofilm formation by B. subtilis by interfering with the aggregation and amyloid formation by TasA (28-261) –TapA (33-253) . These results represent one of the first experimental evidences for the underlying mechanism of antibiofilm activity of statins and offer valuable directions for future research to harness statins as antibiofilm therapeutics. Applied Biochemistry Bacillus subtilis Biofilms Statins Antibiofilm activity Mode of Action Inhibition of amyloid formation Gene Expression Analysis Full Text Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 1 posted 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. 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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-4499575","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":308418759,"identity":"ab853dc6-7d77-40c6-b3da-5f47538487cb","order_by":0,"name":"Nidhi Verma","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Nidhi","middleName":"","lastName":"Verma","suffix":""},{"id":308418975,"identity":"6116155e-e4b7-460c-929d-3eab980e031e","order_by":1,"name":"Mamta 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Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Bacillus subtilis, Biofilms, Statins, Antibiofilm activity, Mode of Action, Inhibition of amyloid formation, Gene Expression Analysis","lastPublishedDoi":"10.21203/rs.3.rs-4499575/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4499575/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eStatins have been reported for diverse pleiotropic activities, including antimicrobial and antibiofilm. However, due to the limited understanding of their mode of action, none of the statins have gained approval for antimicrobial or antibiofilm applications. In a recent drug-repurposing study, we observed that two statins (i.e., Simvastatin and Lovastatin) interact stably with TasA\u003csub\u003e(28-261)\u003c/sub\u003e, the principal extracellular matrix protein of \u003cem\u003eBacillus subtilis\u003c/em\u003e, leading to the inhibition of biofilm formation. Nevertheless, the precise mechanism underlying the biofilm inhibition remained elusive. In the present study, we examined the impact of these statins on the physiological activity of TasA\u003csub\u003e(28-261\u003c/sub\u003e, specifically its interaction with TapA\u003csub\u003e(33-253)\u003c/sub\u003e and aggregation into the amyloid-like structure using purified recombinant TasA\u003csub\u003e(28-261)\u003c/sub\u003e and TapA\u003csub\u003e(33-253)\u003c/sub\u003e in amyloid detection specific \u003cem\u003ein vitro\u003c/em\u003e assays (i.e., CR binding \u0026amp; ThT staining assays). Results revealed that both statins interfered with amyloid formation by TasA\u003csub\u003e(28-261)\u003c/sub\u003e-TapA\u003csub\u003e(33-253)\u003c/sub\u003e complex, while neither statin inhibited amyloid formation by lysozyme, a model amyloid-forming protein. Moreover, neither statin significantly altered the expressions of terminal regulatory genes (viz., \u003cem\u003esinR\u003c/em\u003e, \u003cem\u003esinI\u003c/em\u003e) and effector genes (viz.,\u003cem\u003e tasA\u003c/em\u003e, \u003cem\u003etapA\u003c/em\u003e, and \u003cem\u003ebslA\u003c/em\u003e) involved in biofilm formation by \u003cem\u003eB. subtilis.\u003c/em\u003e These findings divulge that Simvastatin and Lovastatin inhibit biofilm formation by \u003cem\u003eB. subtilis\u003c/em\u003e by interfering with the aggregation and amyloid formation by TasA\u003csub\u003e(28-261)\u003c/sub\u003e–TapA\u003csub\u003e(33-253)\u003c/sub\u003e. These results represent one of the first experimental evidences for the underlying mechanism of antibiofilm activity of statins and offer valuable directions for future research to harness statins as antibiofilm therapeutics.\u003c/p\u003e","manuscriptTitle":"Simvastatin and Lovastatin inhibit Bacillus subtilis biofilm formation by interfering with the aggregation and amyloid formation of the TasA(28-261) –TapA(33-253) complex.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-31 03:23:06","doi":"10.21203/rs.3.rs-4499575/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"14ee3f04-de11-455a-b6da-9a566a48b241","owner":[],"postedDate":"May 31st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":32581010,"name":"Applied Biochemistry"}],"tags":[],"updatedAt":"2024-05-31T03:23:06+00:00","versionOfRecord":[],"versionCreatedAt":"2024-05-31 03:23:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4499575","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4499575","identity":"rs-4499575","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}