{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:42:04Z","timestamp":1785404524304,"version":"3.56.0"},"posted":{"date-parts":[[2026,7,6]]},"group-title":"Biochemistry","reference-count":36,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R01GM118651-09"],"award-info":[{"award-number":["R01GM118651-09"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100032490","name":"Freedom Together Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100032490","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Protein misfolding and aggregation, including amyloid fibril formation, underlie a large class of human diseases including prominent neurological disorders such as Alzheimer\u2019s and Parkinson\u2019s disease. A small number of human proteins have been identified that inhibit amyloidogenesis. One such protein is sTREM2, a soluble receptor liberated from microglia, the resident macrophages of the central nervous system. The extracellular domain of TREM2 is shed upon proteolytic cleavage to create sTREM2, which has previously been shown to inhibit amyloid-\u03b2 aggregation\n                  <jats:italic>in vitro<\/jats:italic>\n                  . TREM2 is also expressed by intestinal macrophages, which are known to directly bind the bacterial amyloid curli and mount cytokine responses upon exposure. Here we show that sTREM2 is a sub-stoichiometric inhibitor of CsgA amyloidogenesis, CsgA being the major protein component of curli that drives biofilm formation in uropathogenic\n                  <jats:italic>Escherichia coli<\/jats:italic>\n                  and many other proteobacteria.\n                  <jats:italic>In vitro<\/jats:italic>\n                  , sTREM2 potently and sub-stoichiometrically inhibited CsgA amyloidogenesis in a dose-dependent manner. Kinetic modeling indicated that sTREM2 slowed primary and secondary nucleation, rather than altering fiber elongation. When added exogenously to bacterial growth medium, sTREM2 significantly suppressed curli-dependent pellicle biofilm formation without affecting bacterial growth. These findings establish sTREM2 as a member of the small group of human proteins capable of inhibiting bacterial functional amyloidogenesis, suggesting that gut-resident TREM2-expressing macrophages, which are already known to interact with curli, may employ sTREM2 as a physiologically relevant defense against bacterial amyloid formation.\n                <\/jats:p>","DOI":"10.64898\/2026.07.03.736422","type":"posted-content","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T10:25:25Z","timestamp":1783333525000},"source":"Crossref","is-referenced-by-count":0,"title":["The Microglial Protein sTREM2 Inhibits the Bacterial Functional Amyloid CsgA and Suppresses Amyloid-Dependent Biofilm Formation"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7409-7031","authenticated-orcid":false,"given":"Anthony","family":"Balistreri","sequence":"first","affiliation":[{"name":"Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Gomulinski","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2645-1294","authenticated-orcid":false,"given":"Matthew R.","family":"Chapman","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8943-3395","authenticated-orcid":false,"given":"Jeffery W.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026070805352840000_2026.07.03.736422v1.1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-061516-045115"},{"key":"2026070805352840000_2026.07.03.736422v1.2","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1039\/D1SC05790A","article-title":"Chaperones mainly suppress primary nucleation during formation of functional amyloid required for bacterial biofilm formation","volume":"13","year":"2022","journal-title":"Chemical Science"},{"key":"2026070805352840000_2026.07.03.736422v1.3","doi-asserted-by":"crossref","unstructured":"A. L. Gharibyan , S. Wasana Jayaweera , M. Lehmann , I. Anan , A. Olofsson , Endogenous Human Proteins Interfering with Amyloid Formation. Biomolecules 12, 446 (2022).","DOI":"10.3390\/biom12030446"},{"key":"2026070805352840000_2026.07.03.736422v1.4","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-7986com"},{"key":"2026070805352840000_2026.07.03.736422v1.5","doi-asserted-by":"publisher","DOI":"10.1080\/1040841X.2022.2146481"},{"key":"2026070805352840000_2026.07.03.736422v1.6","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s13024-025-00834-z","article-title":"TREM2 and sTREM2 in Alzheimer\u2019s disease: from mechanisms to therapies","volume":"20","year":"2025","journal-title":"Mol. Neurodegener"},{"key":"2026070805352840000_2026.07.03.736422v1.7","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn217"},{"key":"2026070805352840000_2026.07.03.736422v1.8","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.517540"},{"key":"2026070805352840000_2026.07.03.736422v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.100631"},{"key":"2026070805352840000_2026.07.03.736422v1.10","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0803343106"},{"key":"2026070805352840000_2026.07.03.736422v1.11","doi-asserted-by":"crossref","first-page":"eadi5374","DOI":"10.1126\/sciimmunol.adi5374","article-title":"TREM2 deficiency reprograms intestinal macrophages and microbiota to enhance anti-PD-1 tumor immunotherapy","volume":"9","year":"2024","journal-title":"Sci Immunol"},{"key":"2026070805352840000_2026.07.03.736422v1.12","doi-asserted-by":"crossref","unstructured":"S. A. Tursi , \u00c7. T\u00fckel , Curli-Containing Enteric Biofilms Inside and Out: Matrix Composition, Immune Recognition, and Disease Implications. Microbiol Mol Biol Rev 82 (2018).","DOI":"10.1128\/MMBR.00028-18"},{"key":"2026070805352840000_2026.07.03.736422v1.13","doi-asserted-by":"publisher","DOI":"10.1126\/science.1067484"},{"key":"2026070805352840000_2026.07.03.736422v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2011.05.015"},{"key":"2026070805352840000_2026.07.03.736422v1.15","doi-asserted-by":"publisher","DOI":"10.1021\/bi011194d"},{"key":"2026070805352840000_2026.07.03.736422v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2014.12.025"},{"key":"2026070805352840000_2026.07.03.736422v1.17","doi-asserted-by":"crossref","unstructured":"J. D. Taylor et al., Electrostatically-guided inhibition of Curli amyloid nucleation by the CsgC-like family of chaperones. 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