{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T23:23:02Z","timestamp":1781306582640,"version":"3.54.1"},"reference-count":57,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T00:00:00Z","timestamp":1725580800000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82160664"],"award-info":[{"award-number":["82160664"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["mLife"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Quorum sensing (QS) inhibition has emerged as a promising target for directed drug design, providing an appealing strategy for developing antimicrobials, particularly against infections caused by drug\u2010resistant pathogens. In this study, we designed and synthesized a total of 33 \u03b2\u2010nitrostyrene derivatives using 1\u2010nitro\u20102\u2010phenylethane (NPe) as the lead compound, to target the facultative anaerobic bacterial pathogen <jats:italic>Serratia marcescens<\/jats:italic>. The QS\u2010inhibitory effects of these compounds were evaluated using <jats:italic>S. marcescens<\/jats:italic> NJ01 and the reporter strain <jats:italic>Chromobacterium violaceum<\/jats:italic> CV026. Among the 33 new \u03b2\u2010nitrostyrene derivatives, (<jats:italic>E<\/jats:italic>)\u20101\u2010methyl\u20104\u2010(2\u2010nitrovinyl)benzene (m\u2010NPe, compound 28) was proven to be a potent inhibitor that reduced biofilm formation of <jats:italic>S. marcescens<\/jats:italic> NJ01 by 79%. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) results revealed that treatment with m\u2010NPe (50\u2009\u03bcg\/ml) not only enhanced the susceptibility of the formed biofilms but also disrupted the architecture of biofilms by 84%. m\u2010NPe (50\u2009\u03bcg\/ml) decreased virulence factors in <jats:italic>S. marcescens<\/jats:italic> NJ01, reducing the activity of protease, prodigiosin, and extracellular polysaccharide (EPS) by 36%, 72%, and 52%, respectively. In <jats:italic>S. marcescens<\/jats:italic> 4547, the activities of hemolysin and EPS were reduced by 28% and 40%, respectively, outperforming the positive control, vanillic acid (VAN). The study also found that the expression levels of QS\u2010 and biofilm\u2010related genes (<jats:italic>flhD, fimA, fimC, sodB, bsmB, pigA, pigC<\/jats:italic>, and <jats:italic>shlA<\/jats:italic>) were downregulated by 1.21\u2010 to 2.32\u2010fold. Molecular dynamics analysis showed that m\u2010NPe could bind stably to SmaR, RhlI, RhlR, LasR, and CviR proteins in a 0.1\u2009M sodium chloride solution. Importantly, a microscale thermophoresis (MST) test revealed that SmaR could be a target protein for the screening of a quorum sensing inhibitor (QSI) against <jats:italic>S. marcescens<\/jats:italic>. Overall, this study highlights the efficacy of m\u2010NPe in suppressing the virulence factors of <jats:italic>S. marcescens<\/jats:italic>, identifying it as a new potential QSI and antibiofilm agent capable of restoring or improving antimicrobial drug sensitivity.<\/jats:p>","DOI":"10.1002\/mlf2.12135","type":"journal-article","created":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T12:11:29Z","timestamp":1725624689000},"page":"445-458","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Discovery of \u03b2\u2010nitrostyrene derivatives as potential quorum sensing inhibitors for biofilm inhibition and antivirulence factor therapeutics against <i>Serratia marcescens<\/i>"],"prefix":"10.1002","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3270-020X","authenticated-orcid":false,"given":"Jiang","family":"Wang","sequence":"first","affiliation":[{"name":"Hainan Affiliated Hospital of Hainan Medical University Hainan General Hospital Haikou China"},{"name":"Center for Translational Research Shenzhen Bay Laboratory Shenzhen China"},{"name":"Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences Hainan University Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences Hainan University Haikou China"},{"name":"Hainan Branch, Shanghai Children's Medical Center, School of Medicine Shanghai Jiao Tong University Sanya China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6312-6589","authenticated-orcid":false,"given":"Pradeepraj","family":"Durairaj","sequence":"additional","affiliation":[{"name":"Center for Translational Research Shenzhen Bay Laboratory Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences Hainan University Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongyan","family":"Wei","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences Hainan University Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi","family":"Tang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences Hainan University Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiqing","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences Hainan University Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2086-1663","authenticated-orcid":false,"given":"Dayong","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences Hainan University Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8089-6200","authenticated-orcid":false,"given":"Ai\u2010Qun","family":"Jia","sequence":"additional","affiliation":[{"name":"Hainan Affiliated Hospital of Hainan Medical University Hainan General Hospital Haikou China"},{"name":"Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences Hainan University Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,6]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41570-021-00313-1"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)02724-0"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.12998\/wjcc.v3.i7.575"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1086\/653053"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.28803-0"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2018.04.023"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1531"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2012.03.063"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-020-10593-0"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.01829-22"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.synbio.2021.09.010"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.9b01005"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/08927014.2021.1874942"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/femspd\/ftv038"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-16507-x"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2011.06.072"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg366"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2020.104376"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo01094a050"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2006.02.006"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22020613"},{"key":"e_1_2_10_23_1","first-page":"406","article-title":"Color me bad: microbial pigments as virulence factors","volume":"17","author":"Liu GY","year":"2009","journal-title":"TIM"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/08927014.2014.972386"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep02935"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00284-009-9564-y"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00859-07"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1128\/jb.179.2.382-388.1997"},{"key":"e_1_2_10_29_1","first-page":"1","article-title":"Effects of PNPG on cell growth cycle, motility machinery and quorum sensing in Serratia marcescens","volume":"37","author":"Wei J\u2010R","year":"2004","journal-title":"J Microbiol Immunol Infect"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02256408"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2017.00498"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2011.04.003"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.5539\/ijc.v5n4p9"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms9051083"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s42770-021-00465-8"},{"key":"e_1_2_10_36_1","first-page":"619","article-title":"Quorum sensing inhibitors: how strong is the evidence?","volume":"21","author":"Defoirdt T","year":"2013","journal-title":"TIM"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.3c00433"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.2217\/17460913.2.6.605"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodres.2011.10.022"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.186.3.692-698.2004"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2014.02.008"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2017.01865"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijfoodmicro.2014.11.028"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-012-4674-z"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10482-017-0971-y"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.46798\/ijam.2018.v21i01.004"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1021\/bm800600p"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.584812"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2003.03295.x"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-9601-8_3"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00566-07"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micres.2022.127102"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1314415110"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt055"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-15976-8"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.softx.2015.06.001"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15816"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11356-022-24957-8"}],"container-title":["mLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mlf2.12135","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T03:07:31Z","timestamp":1729739251000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mlf2.12135"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9]]},"references-count":57,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["10.1002\/mlf2.12135"],"URL":"https:\/\/doi.org\/10.1002\/mlf2.12135","archive":["Portico"],"relation":{},"ISSN":["2097-1699","2770-100X"],"issn-type":[{"value":"2097-1699","type":"print"},{"value":"2770-100X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9]]},"assertion":[{"value":"2024-01-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}