{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T16:51:10Z","timestamp":1776185470482,"version":"3.50.1"},"reference-count":78,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T00:00:00Z","timestamp":1693958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007076","name":"Associazione Italiana Ricerca sul Cancro (AIRC)","doi-asserted-by":"publisher","award":["21147"],"award-info":[{"award-number":["21147"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007076","name":"Associazione Italiana Ricerca sul Cancro (AIRC)","doi-asserted-by":"publisher","award":["IG-2019 N. 23465"],"award-info":[{"award-number":["IG-2019 N. 23465"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007076","name":"Associazione Italiana Ricerca sul Cancro (AIRC)","doi-asserted-by":"publisher","award":["PE00000007, INF-ACT"],"award-info":[{"award-number":["PE00000007, INF-ACT"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Regulatory pathways of myeloid cells, inflammation and cancer","award":["21147"],"award-info":[{"award-number":["21147"]}]},{"name":"Regulatory pathways of myeloid cells, inflammation and cancer","award":["IG-2019 N. 23465"],"award-info":[{"award-number":["IG-2019 N. 23465"]}]},{"name":"Regulatory pathways of myeloid cells, inflammation and cancer","award":["PE00000007, INF-ACT"],"award-info":[{"award-number":["PE00000007, INF-ACT"]}]},{"name":"NextGenerationEU-MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases","award":["21147"],"award-info":[{"award-number":["21147"]}]},{"name":"NextGenerationEU-MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases","award":["IG-2019 N. 23465"],"award-info":[{"award-number":["IG-2019 N. 23465"]}]},{"name":"NextGenerationEU-MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases","award":["PE00000007, INF-ACT"],"award-info":[{"award-number":["PE00000007, INF-ACT"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>The recognition of microbe and extracellular matrix (ECM) is a recurring theme in the humoral innate immune system. Fluid-phase molecules of innate immunity share regulatory roles in ECM. On the other hand, ECM elements have immunological functions. Innate immunity is evolutionary and functionally connected to hemostasis. Staphylococcus aureus (S. aureus) is a major cause of hospital-associated bloodstream infections and the most common cause of several life-threatening conditions such as endocarditis and sepsis through its ability to manipulate hemostasis. Biofilm-related infection and sepsis represent a medical need due to the lack of treatments and the high resistance to antibiotics. We designed a method combining imaging and microfluidics to dissect the role of elements of the ECM and hemostasis in triggering S. aureus biofilm by highlighting an essential role of fibrinogen (FG) in adhesion and formation. Furthermore, we ascertained an important role of the fluid-phase activation of fibrinolysis in inhibiting biofilm of S. aureus and facilitating an antibody-mediated response aimed at pathogen killing. The results define FG as an essential element of hemostasis in the S. aureus biofilm formation and a role of fibrinolysis in its inhibition, while promoting an antibody-mediated response. Understanding host molecular mechanisms influencing biofilm formation and degradation is instrumental for the development of new combined therapeutic approaches to prevent the risk of S. aureus biofilm-associated diseases.<\/jats:p>","DOI":"10.3390\/pathogens12091141","type":"journal-article","created":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T10:07:37Z","timestamp":1693994857000},"page":"1141","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A Multilayered Imaging and Microfluidics Approach for Evaluating the Effect of Fibrinolysis in Staphylococcus aureus Biofilm Formation"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3607-1380","authenticated-orcid":false,"given":"Raffaella","family":"Parente","sequence":"first","affiliation":[{"name":"Multiscale ImmunoImaging Unit (mIIu), IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3404-5779","authenticated-orcid":false,"given":"Maria Rita","family":"Fumagalli","sequence":"additional","affiliation":[{"name":"Multiscale ImmunoImaging Unit (mIIu), IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2108-3008","authenticated-orcid":false,"given":"Alessia","family":"Di Claudio","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cindy Lorena","family":"C\u00e1rdenas Rinc\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1922-0818","authenticated-orcid":false,"given":"Marco","family":"Erreni","sequence":"additional","affiliation":[{"name":"Multiscale ImmunoImaging Unit (mIIu), IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Italy"},{"name":"Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Damiano","family":"Zanini","sequence":"additional","affiliation":[{"name":"Multiscale ImmunoImaging Unit (mIIu), IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7972-1569","authenticated-orcid":false,"given":"Giacomo","family":"Iapichino","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Intensive Care Units, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Protti","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Italy"},{"name":"Department of Anesthesia and Intensive Care Units, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1510-7703","authenticated-orcid":false,"given":"Cecilia","family":"Garlanda","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Italy"},{"name":"IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8385-9296","authenticated-orcid":false,"given":"Roberto","family":"Rusconi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Italy"},{"name":"IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Doni","sequence":"additional","affiliation":[{"name":"Multiscale ImmunoImaging Unit (mIIu), IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1160\/TH07-02-0117","article-title":"Fibrinolysis and host response in bacterial infections","volume":"98","author":"Bergmann","year":"2007","journal-title":"Thromb. 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