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However, there is a risk that suppression of the staphylococcal QS Agr system might promote biofilm formation. In this study, we found that both Agr activity and the biofilm of\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    can be reduced by a sappanwood extract (SWe). The impaired biofilm in the presence of SWe exhibited reduced extracellular DNA (eDNA) and increased extracellular polysaccharides. SWe also reduced pigmentation. The RNA\u2010seq analysis showed that SWe suppressed multiple key virulence regulators, including the Agr and SaeRS systems. SWe downregulated cell\u2010wall\u2010associated proteins and several Agr\u2010regulated virulence factors such as hemolysins and phenol\u2010soluble modulins (PSMs). The present study did not intend the clinical application of the SWe but exemplified that it is possible to suppress multiple virulence phenotypes simultaneously\n                    <jats:italic>in vitro<\/jats:italic>\n                    , suggesting a new therapeutic concept to combat\n                    <jats:italic>S. aureus<\/jats:italic>\n                    infection.\n                  <\/jats:p>","DOI":"10.1002\/mbo3.70380","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T05:07:56Z","timestamp":1789362476000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multifaceted Suppression of Staphylococcal Virulence Phenotypes:\n                    <i>In Vitro<\/i>\n                    Study of a Cellular Status With Reduced Agr Activity and Impaired Biofilm"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-1807-2067","authenticated-orcid":false,"given":"Nghi Bao","family":"Nguyen","sequence":"first","affiliation":[{"name":"Graduate School of Comprehensive Human Sciences University of Tsukuba Tsukuba Japan"},{"name":"Center for Molecular Biomedicine University of Medicine and Pharmacy at HCMC HCM City Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4169-315X","authenticated-orcid":false,"given":"Yuri","family":"Ushijima","sequence":"additional","affiliation":[{"name":"Division of Biomedical Science, Institute of Medicine University of Tsukuba Tsukuba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7015-7869","authenticated-orcid":false,"given":"Raiku","family":"Sekiya","sequence":"additional","affiliation":[{"name":"Graduate School of Comprehensive Human Sciences University of Tsukuba Tsukuba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1503-7151","authenticated-orcid":false,"given":"Kazuya","family":"Morikawa","sequence":"additional","affiliation":[{"name":"Division of Biomedical Science, Institute of Medicine University of Tsukuba Tsukuba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4082-0896","authenticated-orcid":false,"given":"Le Thuy Thi","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Biotechnology Centre of Ho Chi Minh City, Trung My Tay Ward HCM City Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,13]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/LIFE13030703"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/JOURNAL.PONE.0041415"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/J.1574-6968.2006.00281.X"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000052"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0077122"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/IJMS22169100"},{"issue":"12","key":"e_1_2_10_8_1","first-page":"1123","article-title":"Four Pediatric Deaths From Community\u2010Acquired Methicillin\u2010Resistant Staphylococcus aureus\u2014Minnesota and North Dakota, 1997\u20101999","volume":"282","author":"CDC","year":"1999","journal-title":"Journal of the American Medical Association (Chicago, IL)"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fsi.2025.110691"},{"key":"e_1_2_10_10_1","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/978-3-319-07212-8_3","volume-title":"Statistical Analysis of Next Generation Sequencing Data","author":"Chen Y.","year":"2014"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41522-022-00278-z"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/1751-7915.12155"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00204-06\/ASSET\/0B500F87-F8F6-43EC-8C7E-02D1C33F109E\/ASSETS\/GRAPHIC\/ZII0080661110005.JPEG"},{"key":"e_1_2_10_14_1","unstructured":"CLSI M26\u2010A. n.d.\u2010 Methods for Determining Bactericidal Activity of Antimicrobial Agents; Approved Guideline. 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