Staphylococcus aureus PSMα1 amyloid structure is modulated by buffer and salt

Staphylococcus aureus PSMα1 amyloid structure is modulated by buffer and salt | 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 Article Staphylococcus aureus PSMα1 amyloid structure is modulated by buffer and salt Emilie Buhl Plechinger, Kasper Holst Hansen, Qian Liu, Ümit Akbey, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8956596/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Amyloid fibrils share a characteristic cross-β structure yet often display pronounced polymorphism, where a single protein or peptide sequence can adopt multiple distinct fibrillar architectures. Environmental factors such as buffer composition, ionic strength, and pH strongly influence amyloid assembly, modulating fibril morphology, stability, and function. In Staphylococcus aureus , phenol-soluble modulins (PSMs) are key contributors to biofilm integrity and pathogenicity, with PSMα1 forming stable fibrils that reinforce the biofilm matrix. However, the influence of the physicochemical environment on PSMα1 aggregation remains poorly defined. Here, we systematically examine how solution conditions, ionic strength, and cross-seeding modulate PSMα1 fibril formation. Our results show that variations in these parameters markedly alter aggregation kinetics, fibril morphology, hydrophobic surface exposure, and molecular organization. Distinct buffer conditions promote the emergence of different fibrillar polymorphs, reflecting the environmental sensitivity observed in disease-associated amyloids. These findings underscore the critical role of the solution environment in directing amyloid assembly pathways and suggest that environmentally driven fibril polymorphism may contribute to S. aureus biofilm stability and pathogenic behavior. Biological sciences/Biochemistry Biological sciences/Biophysics Physical sciences/Materials science Biological sciences/Microbiology Functional amyloids Protein aggregation Phenol-soluble modulins Aggregate polymorphism Full Text Additional Declarations No competing interests reported. Supplementary Files Supplementaryinformation.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 29 Apr, 2026 Reviews received at journal 16 Apr, 2026 Reviewers agreed at journal 20 Mar, 2026 Reviewers agreed at journal 19 Mar, 2026 Reviewers agreed at journal 18 Mar, 2026 Reviewers invited by journal 17 Mar, 2026 Editor assigned by journal 17 Mar, 2026 Editor invited by journal 02 Mar, 2026 Submission checks completed at journal 27 Feb, 2026 First submitted to journal 27 Feb, 2026 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-8956596","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":608158836,"identity":"f49a523a-15de-4676-9d8c-8feec97ceb69","order_by":0,"name":"Emilie Buhl Plechinger","email":"","orcid":"","institution":"Aarhus University","correspondingAuthor":false,"prefix":"","firstName":"Emilie","middleName":"Buhl","lastName":"Plechinger","suffix":""},{"id":608158837,"identity":"0f142bd7-c1e6-48f0-a824-c84afb1b664f","order_by":1,"name":"Kasper Holst Hansen","email":"","orcid":"","institution":"Aarhus University","correspondingAuthor":false,"prefix":"","firstName":"Kasper","middleName":"Holst","lastName":"Hansen","suffix":""},{"id":608158838,"identity":"af804c5c-b17d-4349-8ada-03e66dd020ed","order_by":2,"name":"Qian Liu","email":"","orcid":"","institution":"Aarhus University","correspondingAuthor":false,"prefix":"","firstName":"Qian","middleName":"","lastName":"Liu","suffix":""},{"id":608158839,"identity":"13998e21-c178-4100-95f2-4ec8cd988814","order_by":3,"name":"Ümit Akbey","email":"","orcid":"","institution":"University of Pittsburgh","correspondingAuthor":false,"prefix":"","firstName":"Ümit","middleName":"","lastName":"Akbey","suffix":""},{"id":608158840,"identity":"01e4492e-8507-404f-8859-7bfde3e8f4d3","order_by":4,"name":"Maria Andreasen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA20lEQVRIiWNgGAWjYJCCAww8NglsIBYPmJ9GlJY0ErUAweEEBqK16LaffXjgh8z5PD727sQHbxjsEhvY0xLwajE7k25wsIfndjEbz9nNhnMYkhMbeJ4dwK/lQBrDAR6e24ltErnbpHkYmBMbJNIb8Gs5/4zh4B+ecyAt23/zMNQToeVGGsNhHp4DYFuYeRgOA7WkEXDYjWcMh2V4ksF+kZxjcNy4jedZAgGHpTF/fNtjlyff3rvxw5uKatl+9jQDvFrAgLEHxgIqZiOsHgR+EKdsFIyCUTAKRigAAIbYR+Joqhg/AAAAAElFTkSuQmCC","orcid":"","institution":"Aarhus University","correspondingAuthor":true,"prefix":"","firstName":"Maria","middleName":"","lastName":"Andreasen","suffix":""}],"badges":[],"createdAt":"2026-02-24 11:08:38","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8956596/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8956596/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":105035590,"identity":"fc6653ac-dc98-42f1-8980-c35ab643cfb8","added_by":"auto","created_at":"2026-03-20 07:26:17","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1631886,"visible":true,"origin":"","legend":"","description":"","filename":"StaphylococcusaureusPSM1amyloidstructureismodulatedbybufferandsaltEBP1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8956596/v1_covered_7252d352-f84e-490d-a25d-656a2984bb32.pdf"},{"id":104983983,"identity":"5e606d48-282d-4e9d-881d-999ad476f014","added_by":"auto","created_at":"2026-03-19 14:00:13","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":439493,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementaryinformation.docx","url":"https://assets-eu.researchsquare.com/files/rs-8956596/v1/1e9b0fd98186100b0a4a4fdf.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Staphylococcus aureus PSMα1 amyloid structure is modulated by buffer and salt","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Functional amyloids, Protein aggregation, Phenol-soluble modulins, Aggregate polymorphism","lastPublishedDoi":"10.21203/rs.3.rs-8956596/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8956596/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAmyloid fibrils share a characteristic cross-β structure yet often display pronounced polymorphism, where a single protein or peptide sequence can adopt multiple distinct fibrillar architectures. Environmental factors such as buffer composition, ionic strength, and pH strongly influence amyloid assembly, modulating fibril morphology, stability, and function. In \u003cem\u003eStaphylococcus aureus\u003c/em\u003e, phenol-soluble modulins (PSMs) are key contributors to biofilm integrity and pathogenicity, with PSMα1 forming stable fibrils that reinforce the biofilm matrix. However, the influence of the physicochemical environment on PSMα1 aggregation remains poorly defined. Here, we systematically examine how solution conditions, ionic strength, and cross-seeding modulate PSMα1 fibril formation. Our results show that variations in these parameters markedly alter aggregation kinetics, fibril morphology, hydrophobic surface exposure, and molecular organization. Distinct buffer conditions promote the emergence of different fibrillar polymorphs, reflecting the environmental sensitivity observed in disease-associated amyloids. These findings underscore the critical role of the solution environment in directing amyloid assembly pathways and suggest that environmentally driven fibril polymorphism may contribute to \u003cem\u003eS. aureus\u003c/em\u003e biofilm stability and pathogenic behavior.\u003c/p\u003e","manuscriptTitle":"Staphylococcus aureus PSMα1 amyloid structure is modulated by buffer and salt","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-19 14:00:04","doi":"10.21203/rs.3.rs-8956596/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"1519386041209789622628270404171730609","date":"2026-04-29T10:20:05+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-16T06:42:00+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"160510363159765111076733053820530364645","date":"2026-03-20T05:39:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"62910127950442707760809518941461014467","date":"2026-03-19T15:15:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"328322199720583722355488887261037688237","date":"2026-03-18T09:51:23+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-17T13:21:58+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-17T13:10:38+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-03-02T17:38:07+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-27T22:44:03+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2026-02-27T17:01:19+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"314d8dc7-9fd8-4eee-baec-a5a91d24a7da","owner":[],"postedDate":"March 19th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":64713201,"name":"Biological sciences/Biochemistry"},{"id":64713202,"name":"Biological sciences/Biophysics"},{"id":64713203,"name":"Physical sciences/Materials science"},{"id":64713204,"name":"Biological sciences/Microbiology"}],"tags":[],"updatedAt":"2026-03-19T14:00:05+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-19 14:00:04","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8956596","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8956596","identity":"rs-8956596","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}