{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T22:47:55Z","timestamp":1788821275276,"version":"build-2803163510"},"reference-count":49,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,5,8]],"date-time":"2020-05-08T00:00:00Z","timestamp":1588896000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["PRIN2017 (Grant 2017SFBFER to RZ)"],"award-info":[{"award-number":["PRIN2017 (Grant 2017SFBFER to RZ)"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Pregnadiene-11-hydroxy-16\u03b1,17\u03b1-epoxy-3,20-dione-1 (PYED-1), a heterocyclic corticosteroid derivative of deflazacort, exhibits broad-spectrum antibacterial activity against Gram-negative and Gram-positive bacteria. Here, we investigated the effect of PYED-1 on the biofilms of Staphylococcus aureus, an etiological agent of biofilm-based chronic infections such as osteomyelitis, indwelling medical device infections, periodontitis, chronic wound infections, and endocarditis. PYED-1 caused a strong reduction in biofilm formation in a concentration dependent manner. Furthermore, it was also able to completely remove the preformed biofilm. Transcriptional analysis performed on the established biofilm revealed that PYED-1 downregulates the expression of genes related to quorum sensing (agrA, RNAIII, hld, psm, and sarA), surface proteins (clfB and fnbB), secreted toxins (hla, hlb, and lukD), and capsular polysaccharides (capC). The expression of genes that encode two main global regulators, sigB and saeR, was also significantly inhibited after treatment with PYED-1. In conclusion, PYED-1 not only effectively inhibited biofilm formation, but also eradicated preformed biofilms of S. aureus, modulating the expression of genes related to quorum sensing, surface and secreted proteins, and capsular polysaccharides. These results indicated that PYED-1 may have great potential as an effective antibiofilm agent to prevent S. aureus biofilm-associated infections.<\/jats:p>","DOI":"10.3390\/antibiotics9050240","type":"journal-article","created":{"date-parts":[[2020,5,8]],"date-time":"2020-05-08T11:26:00Z","timestamp":1588937160000},"page":"240","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["PYED-1 Inhibits Biofilm Formation and Disrupts the Preformed Biofilm of Staphylococcus aureus"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1383-3178","authenticated-orcid":false,"given":"Adriana","family":"Vollaro","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0139-8316","authenticated-orcid":false,"given":"Anna","family":"Esposito","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences, University of Naples Federico II, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8872-4211","authenticated-orcid":false,"given":"Eliana Pia","family":"Esposito","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4191-9032","authenticated-orcid":false,"given":"Raffaele","family":"Zarrilli","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8684-0622","authenticated-orcid":false,"given":"Annalisa","family":"Guaragna","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences, University of Naples Federico II, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2529-8611","authenticated-orcid":false,"given":"Eliana","family":"De Gregorio","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1146\/annurev.micro.56.012302.160705","article-title":"Biofilms as complex differentiated communities","volume":"56","author":"Stoodley","year":"2002","journal-title":"Ann. Rev. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/nrmicro2415","article-title":"The biofilm matrix","volume":"8","author":"Flemming","year":"2010","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5142","DOI":"10.1016\/j.watres.2005.09.028","article-title":"Effect of mechanical stress on biofilms challenged by different chemicals","volume":"39","author":"Simoes","year":"2005","journal-title":"Water Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1146\/annurev.micro.57.030502.090720","article-title":"Bacterial biofilms: An emerging link to disease pathogenesis","volume":"57","author":"Parsek","year":"2003","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"824","DOI":"10.3389\/fchem.2019.00824","article-title":"Bacterial Biofilm Eradication Agents: A Current Review","volume":"28","author":"Verderosa","year":"2019","journal-title":"Front. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/apm.12099","article-title":"The role of bacterial biofilms in chronic infections","volume":"136","author":"Bjarnsholt","year":"2013","journal-title":"APMIS Suppl."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1128\/CMR.00134-14","article-title":"Staphylococcus aureus infections: Epidemiology, pathophysiology, clinical manifestations, and management","volume":"28","author":"Tong","year":"2015","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1146\/annurev-med-042711-140023","article-title":"Staphylococcal infections: Mechanisms of biofilm maturation and detachment as critical determinants of pathogenicity","volume":"64","author":"Otto","year":"2013","journal-title":"Annu. Rev. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"178","DOI":"10.3389\/fcimb.2014.00178","article-title":"Staphylococcus aureus biofilms: Recent developments in biofilm dispersal","volume":"4","author":"Lister","year":"2014","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"21519","DOI":"10.1039\/C9RA03673C","article-title":"Expeditious synthesis and preliminary antimicrobial activity of deflazacort and its precursors","volume":"9","author":"Esposito","year":"2019","journal-title":"RSC Adv."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Vollaro, A., Esposito, A., Antonaki, E., Iula, V.D., D\u2019Alonzo, D., Guaragna, A., and De Gregorio, E. (2020). Steroid Derivatives as potential antimicrobial agents against Staphylococcus aureus planktonic cells. Microorganisms, 8.","DOI":"10.3390\/microorganisms8040468"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Esposito, A., Vollaro, A., Esposito, E.P., D\u2019Alonzo, D., Guaragna, A., Zarrilli, R., and De Gregorio, E. (2020). Antibacterial and Antivirulence Activity of Glucocorticoid PYED-1 against Stenotrophomonas maltophilia. Antibiotics (Basel), 9.","DOI":"10.3390\/antibiotics9030105"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1128\/CMR.15.2.167-193.2002","article-title":"Biofilms: Survival mechanisms of clinically relevant microorganisms","volume":"15","author":"Costerton","year":"2002","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"493","DOI":"10.4155\/fmc.15.6","article-title":"Biofilm formation mechanisms and targets for developing antibiofilm agents","volume":"7","author":"Rabin","year":"2015","journal-title":"Future Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1002\/lary.24322","article-title":"Corticosteroids directly reduce Staphylococcus aureus biofilm growth: An in vitro study","volume":"124","author":"Goggin","year":"2014","journal-title":"Laryngoscope"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"87S","DOI":"10.1111\/j.1365-2672.1993.tb04345.x","article-title":"Sensitivity of biofilms to antimicrobial agents","volume":"74","author":"Brown","year":"1993","journal-title":"J. Appl. Bacteriol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1128\/JB.01214-08","article-title":"A fatty acid messenger is responsible for inducing dispersion in microbial biofilms","volume":"191","author":"Davies","year":"2009","journal-title":"J. Bacteriol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1126\/science.284.5418.1318","article-title":"Bacterial biofilms: A common cause of persistent infections","volume":"284","author":"Costerton","year":"1999","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"9868","DOI":"10.1021\/ja9024676","article-title":"A 2-aminobenzimidazole that inhibits and disperses gram-positive biofilms through a zinc-dependent mechanism","volume":"131","author":"Rogers","year":"2009","journal-title":"J. Am. Chem. Soc."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1111\/j.1462-5822.2009.01323.x","article-title":"Evolving concepts in biofilm infections","volume":"11","author":"Stoodley","year":"2009","journal-title":"Cell Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1111\/mmi.13219","article-title":"Extracellular DNA facilitates the formation of functional amyloids in Staphylococcus aureus biofilms","volume":"99","author":"Schwartz","year":"2016","journal-title":"Mol. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e01137-19","DOI":"10.1128\/mBio.01137-19","article-title":"Identification of extracellular DNA-binding proteins in the biofilm matrix","volume":"10","author":"Kavanaugh","year":"2019","journal-title":"mBio"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"341","DOI":"10.3109\/1040841X.2013.841639","article-title":"The role of extracellular DNA in the establishment, maintenance and perpetuation of bacterial biofilms","volume":"41","author":"Okshevsky","year":"2015","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1128\/MMBR.00030-07","article-title":"Molecular control of bacterial death and lysis","volume":"72","author":"Rice","year":"2008","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2468","DOI":"10.1128\/JB.01545-10","article-title":"Staphylococcus aureus CidA and LrgA proteins exhibit holin-like properties","volume":"193","author":"Ranjit","year":"2011","journal-title":"J. Bacteriol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.mib.2011.12.010","article-title":"The control of death and lysis in staphylococcal biofilms: A coordination of physiological signals","volume":"15","author":"Sadykov","year":"2012","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1007\/s00253-014-6076-x","article-title":"Phenotype and expression profile analysis of Staphylococcus aureus biofilms and planktonic cells in response to licochalcone A","volume":"99","author":"Shen","year":"2015","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.micpath.2018.07.027","article-title":"Phenotype and RNA-seq-Based transcriptome profiling of Staphylococcus aureus biofilms in response to tea tree oil","volume":"123","author":"Zhao","year":"2018","journal-title":"Microb. Pathog."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Wang, D., Jin, Q., Xiang, H., Wang, W., Guo, N., Zhang, K., Tang, X., Meng, R., Feng, H., and Liu, L. (2011). Transcriptional and functional analysis of the effects of magnolol: Inhibition of autolysis and biofilms in Staphylococcus aureus. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0026833"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e02724-16","DOI":"10.1128\/AAC.02724-16","article-title":"Downregulation of autolysin-encoding genes by phage-derived lytic proteins inhibits biofilm formation in Staphylococcus aureus","volume":"61","author":"Fernandez","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.4014\/jmb.1609.09053","article-title":"Screening of anti-biofilm compounds from marine-derived fungi and the effects of secalonic acid D on Staphylococcus aureus biofilm","volume":"27","author":"Wang","year":"2017","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Paharik, A.E., and Horswill, A.R. (2016). The staphylococcal biofilm: Adhesins, regulation, and host response. Microbiol. Spectr., 4.","DOI":"10.1128\/microbiolspec.VMBF-0022-2015"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1128\/JB.01242-09","article-title":"Differential target gene activation by the Staphylococcus aureus two-component system saeRS","volume":"192","author":"Mainiero","year":"2010","journal-title":"J. Bacteriol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1086\/598967","article-title":"The SaeR\/S gene regulatory system is essential for innate immune evasion by Staphylococcus aureus","volume":"199","author":"Voyich","year":"2009","journal-title":"J. Infect. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3419","DOI":"10.1128\/JB.01927-07","article-title":"The virulence regulator Sae of Staphylococcus aureus: Promoter activities and response to phagocytosis-related signals","volume":"190","author":"Geiger","year":"2008","journal-title":"J. Bacteriol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Tsang, L.H., Cassat, J.E., Shaw, L.N., Beenken, K.E., and Smeltzer, M.S. (2008). Factors contributing to the biofilm-deficient phenotype of Staphylococcus aureus sarA mutants. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0003361"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2948","DOI":"10.1128\/JB.01517-10","article-title":"Defining the strain-dependent impact of the staphylococcal accessory regulator (sarA) on the alpha-toxin phenotype of Staphylococcus aureus","volume":"193","author":"Zielinska","year":"2011","journal-title":"J. Bacteriol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"14407","DOI":"10.1073\/pnas.0911032107","article-title":"Beta toxin catalyzes formation of nucleoprotein matrix in staphylococcal biofilms","volume":"107","author":"Huseby","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Mrak, L.N., Zielinska, A.K., Beenken, K.E., Mrak, I.N., Atwood, D.N., Griffin, L.M., Lee, C.Y., and Smeltzer, M.S. (2012). saeRS and sarA act synergistically to repress protease production and promote biofilm formation in Staphylococcus aureus. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0038453"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"416","DOI":"10.3389\/fmicb.2015.00416","article-title":"SarA based novel therapeutic candidate against Staphylococcus aureus associated with vascular graft infections","volume":"6","author":"Arya","year":"2015","journal-title":"Front. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.3389\/fmicb.2017.01290","article-title":"Staphylococcus aureus quorum regulator SarA targeted compound, 2-[(Methylamino) methyl] phenol inhibits biofilm and down-regulates virulence genes","volume":"8","author":"Balamurugan","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1128\/IAI.00046-11","article-title":"Role of the accessory gene regulator agr in community-associated methicillin-resistant Staphylococcus aureus pathogenesis","volume":"79","author":"Cheung","year":"2011","journal-title":"Infect. Immun."},{"key":"ref_43","first-page":"5171","article-title":"Influence of a functional sigB operon on the global regulators sar and agr in Staphylococcus aureus","volume":"83","author":"Bischoff","year":"2011","journal-title":"J. Bacteriol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1128\/IAI.01036-08","article-title":"Interconnections between Sigma B, agr, and proteolytic activity in Staphylococcus aureus biofilm maturation","volume":"77","author":"Lauderdale","year":"2009","journal-title":"Infect. Immun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1128\/CMR.17.1.218-234.2004","article-title":"Staphylococcus aureus capsular polysaccharides","volume":"17","author":"Lee","year":"2004","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.1021\/acssynbio.8b00084","article-title":"Identification of novel cryptic multifunctional antimicrobial peptides from the human stomach enabled by a computational-experimental platform","volume":"7","author":"Pane","year":"2018","journal-title":"ACS Synth. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1007\/s00284-018-1540-y","article-title":"Contact-dependent growth inhibition proteins in Acinetobacter baylyi ADP1","volume":"75","author":"Esposito","year":"2018","journal-title":"Curr. Microbiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1111\/lam.12537","article-title":"Accurate identification of members of the Burkholderia cepacia complex in cystic fibrosis sputum","volume":"62","author":"Martinucci","year":"2016","journal-title":"Lett. Appl. Microbiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/9\/5\/240\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:26:48Z","timestamp":1760174808000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/9\/5\/240"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,8]]},"references-count":49,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,5]]}},"alternative-id":["antibiotics9050240"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics9050240","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,8]]}}}