{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T07:33:54Z","timestamp":1767598434672,"version":"build-2065373602"},"reference-count":65,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,18]],"date-time":"2022-03-18T00:00:00Z","timestamp":1647561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001352","name":"National University of Singapore","doi-asserted-by":"publisher","award":["N571000016001"],"award-info":[{"award-number":["N571000016001"]}],"id":[{"id":"10.13039\/501100001352","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The presence of co-infections or superinfections with bacterial pathogens in COVID-19 patients is associated with poor outcomes, including increased morbidity and mortality. We hypothesized that SARS-CoV-2 and its components interact with the biofilms generated by commensal bacteria, which may contribute to co-infections. This study employed crystal violet staining and particle-tracking microrheology to characterize the formation of biofilms by Streptococcus pneumoniae and Staphylococcus aureus that commonly cause secondary bacterial pneumonia. Microrheology analyses suggested that these biofilms were inhomogeneous soft solids, consistent with their dynamic characteristics. Biofilm formation by both bacteria was significantly inhibited by co-incubation with recombinant SARS-CoV-2 spike S1 subunit and both S1 + S2 subunits, but not with S2 extracellular domain nor nucleocapsid protein. Addition of spike S1 and S2 antibodies to spike protein could partially restore bacterial biofilm production. Furthermore, biofilm formation in vitro was also compromised by live murine hepatitis virus, a related beta-coronavirus. Supporting data from LC-MS-based proteomics of spike\u2013biofilm interactions revealed differential expression of proteins involved in quorum sensing and biofilm maturation, such as the AI-2E family transporter and LuxS, a key enzyme for AI-2 biosynthesis. Our findings suggest that these opportunistic pathogens may egress from biofilms to resume a more virulent planktonic lifestyle during coronavirus infections. The dispersion of pathogens from biofilms may culminate in potentially severe secondary infections with poor prognosis. Further detailed investigations are warranted to establish bacterial biofilms as risk factors for secondary pneumonia in COVID-19 patients.<\/jats:p>","DOI":"10.3390\/ijms23063291","type":"journal-article","created":{"date-parts":[[2022,3,20]],"date-time":"2022-03-20T21:30:14Z","timestamp":1647811814000},"page":"3291","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["SARS-CoV-2 Spike Protein and Mouse Coronavirus Inhibit Biofilm Formation by Streptococcus pneumoniae and Staphylococcus aureus"],"prefix":"10.3390","volume":"23","author":[{"given":"Mun Fai","family":"Loke","sequence":"first","affiliation":[{"name":"Infectious Diseases Translational Research Program, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Indresh","family":"Yadav","sequence":"additional","affiliation":[{"name":"Department of Physics, Faculty of Science, National University of Singapore, Singapore 117542, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teck Kwang","family":"Lim","sequence":"additional","affiliation":[{"name":"Protein and Proteomics Centre, Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore 117558, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5560-0298","authenticated-orcid":false,"given":"Johan R. C.","family":"van der Maarel","sequence":"additional","affiliation":[{"name":"Department of Physics, Faculty of Science, National University of Singapore, Singapore 117542, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lok-To","family":"Sham","sequence":"additional","affiliation":[{"name":"Infectious Diseases Translational Research Program, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2634-6213","authenticated-orcid":false,"given":"Vincent T.","family":"Chow","sequence":"additional","affiliation":[{"name":"Infectious Diseases Translational Research Program, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.jmii.2020.05.013","article-title":"Co-infections among patients with COVID-19: The need for combination therapy with non-anti-SARS-CoV-2 agents?","volume":"53","author":"Lai","year":"2020","journal-title":"J. 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