{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T01:28:54Z","timestamp":1780450134673,"version":"3.54.1"},"reference-count":51,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,3,2]],"date-time":"2020-03-02T00:00:00Z","timestamp":1583107200000},"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)"],"award-info":[{"award-number":["PRIN2017 (Grant 2017SFBFER)"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Stenotrophomonas maltophilia, an environmental Gram-negative bacterium, is an emerging nosocomial opportunistic pathogen that causes life-threatening infections in immunocompromised patients and chronic pulmonary infections in cystic fibrosis patients. Due to increasing resistance to multiple classes of antibiotics, S. maltophilia infections are difficult to treat successfully. This makes the search for new antimicrobial strategies mandatory. In this study, the antibacterial activity of the heterocyclic corticosteroid deflazacort and several of its synthetic precursors was tested against S. maltophilia. All compounds were not active against standard strain S. maltophilia K279a. The compound PYED-1 (pregnadiene-11-hydroxy-16\u03b1,17\u03b1-epoxy-3,20-dione-1) showed a weak effect against some S. maltophilia clinical isolates, but exhibited a synergistic effect with aminoglycosides. PYED-1 at sub-inhibitory concentrations decreased S. maltophilia biofilm formation. Quantitative real-time polymerase chain reaction (RT-qPCR) analysis demonstrated that the expression of biofilm- and virulence- associated genes (StmPr1, StmPr3, sphB, smeZ, bfmA, fsnR) was significantly suppressed after PYED-1 treatment. Interestingly, PYED-1 also repressed the expression of the genes aph (3\u2032)-IIc, aac (6\u2032)-Iz, and smeZ, involved in the resistance to aminoglycosides.<\/jats:p>","DOI":"10.3390\/antibiotics9030105","type":"journal-article","created":{"date-parts":[[2020,3,2]],"date-time":"2020-03-02T07:50:53Z","timestamp":1583135453000},"page":"105","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Antibacterial and Antivirulence Activity of Glucocorticoid PYED-1 against Stenotrophomonas maltophilia"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0139-8316","authenticated-orcid":false,"given":"Anna","family":"Esposito","sequence":"first","affiliation":[{"name":"Department of Chemical Sciences, University of Naples Federico II, Via Cintia, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1383-3178","authenticated-orcid":false,"given":"Adriana","family":"Vollaro","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliana Pia","family":"Esposito","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Naples \u201cFederico II\u201d, Via S. Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2857-8600","authenticated-orcid":false,"given":"Daniele","family":"D\u2019Alonzo","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences, University of Naples Federico II, Via Cintia, 80126 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, Via Cintia, 80126 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 \u201cFederico II\u201d, Via S. Pansini 5, 80131 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, Via S. Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.jinf.2012.01.001","article-title":"Stenotrophomonas maltophilia\u2014the most worrisome threat among unusual non-fermentative gram-negative bacilli from hospitalized patients: A prospective multicenter study","volume":"64","author":"Fihman","year":"2012","journal-title":"J. Infect."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/S1473-3099(09)70083-0","article-title":"Stenotrophomonas maltophilia: An emerging opportunist human pathogen","volume":"9","author":"Looney","year":"2009","journal-title":"Lancet Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1053\/jhin.2002.1280","article-title":"Molecular epidemiology of Stenotrophomonas maltophilia in a university hospital","volume":"52","author":"Crispino","year":"2002","journal-title":"J. Hosp. Infect."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1128\/CMR.00019-11","article-title":"Stenotrophomonas maltophilia: An emerging global opportunistic pathogen","volume":"25","author":"Brooke","year":"2012","journal-title":"Rev. Clin. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e4375","DOI":"10.1097\/MD.0000000000004375","article-title":"Risk factors for mortality in patients with Stenotrophomonas maltophilia bacteremia","volume":"95","author":"Jeon","year":"2016","journal-title":"Medicine"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.jcf.2018.10.011","article-title":"Cystic fibrosis related diabetes is not independently associated with increased Stenotrophomonas maltophilia infection: Longitudinal data from the UK CF Registry","volume":"18","author":"Frost","year":"2019","journal-title":"J. Cyst. Fibros."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1002\/ppul.23781","article-title":"Incident Stenotrophomonas maltophilia infection and lung function decline in cystic fibrosis","volume":"52","author":"Barsky","year":"2017","journal-title":"Pediatr Pulmonol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.jcf.2012.12.006","article-title":"Chronic Stenotrophomonas maltophilia infection and mortality or lung transplantation in cystic fibrosis patients","volume":"12","author":"Waters","year":"2013","journal-title":"J. Cyst. Fibros."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2276","DOI":"10.3389\/fmicb.2017.02276","article-title":"Stenotrophomonas maltophilia as an Emerging Ubiquitous Pathogen: Looking Beyond Contemporary Antibiotic Therapy","volume":"8","author":"Adegoke","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Bayer-Santos, E., Cenens, W., Matsuyama, B.Y., Oka, G.U., Di Sessa, G., Mininel, I., Alves, T., and Farah, C.S. (2019). The opportunistic pathogen Stenotrophomonas maltophilia utilizes a type IV secretion system for interbacterial killing. PLoS Pathog., 15.","DOI":"10.1101\/557322"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1177\/039463200702000311","article-title":"Molecular characterization of virulence determinants of Stenotrophomonas maltophilia strains isolated from patients affected by cystic fibrosis","volume":"20","author":"Prosseda","year":"2007","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e00457-19","DOI":"10.1128\/IAI.00457-19","article-title":"Stenotrophomonas maltophilia encodes a VirB\/VirD4 Type IV Secretion System that modulates apoptosis in human cells and promotes competition against heterologous bacteria, including Pseudomonas aeruginosa","volume":"87","author":"Nas","year":"2019","journal-title":"Infect. Immun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.ijmm.2010.07.003","article-title":"Stenotrophomonas maltophilia strains from cystic fibrosis patients: Genomic variability and molecular characterization of some virulence determinants","volume":"301","author":"Nicoletti","year":"2011","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Pompilio, A., Pomponio, S., Crocetta, V., Gherardi, G., Verginelli, F., Fiscarelli, E., Dicuonzo, G., Savini, V., D\u2019Antonio, D., and Di Bonaventura, G. (2011). Phenotypic and genotypic characterization of Stenotrophomonas maltophilia isolates from patients with cystic fibrosis: Genome diversity, biofilm formation, and virulence. BMC Microbiol., 11.","DOI":"10.1186\/1471-2180-11-159"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1080\/23744235.2018.1531145","article-title":"Stenotrophomonas maltophilia\u2014A low-grade pathogen with numerous virulence factors","volume":"51","author":"Trifonova","year":"2019","journal-title":"Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"893","DOI":"10.3389\/fmicb.2015.00893","article-title":"Update on infections caused by Stenotrophomonas maltophilia with particular attention to resistance mechanisms and therapeutic options","volume":"6","author":"Chang","year":"2015","journal-title":"Front. Microbiol"},{"key":"ref_17","first-page":"658","article-title":"Antibiotic resistance in the opportunistic pathogen Stenotrophomonas maltophilia","volume":"6","year":"2015","journal-title":"Front. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.bjid.2016.04.002","article-title":"Antimicrobial susceptibility of hospital acquired Stenotrophomonas maltophilia isolate biofilms","volume":"20","author":"Sun","year":"2016","journal-title":"Braz. J. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"559","DOI":"10.3201\/eid1304.061378","article-title":"Global emergence of trimethoprim\/sulfamethoxazole resistance in Stenotrophomonas maltophilia mediated by acquisition of sul genes","volume":"13","author":"Toleman","year":"2007","journal-title":"Emerg. Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"fnz069","DOI":"10.1093\/femsle\/fnz069","article-title":"The rpf\/DSF signalling system of Stenotrophomonas maltophilia positively regulates biofilm formation, production of virulence-associated factors and \u03b2-lactamase induction","volume":"366","author":"Alcaraz","year":"2019","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1080\/14787210.2019.1685875","article-title":"Stenotrophomonas maltophilia biofilm: Its role in infectious diseases","volume":"17","year":"2019","journal-title":"Expert. Rev. Anti Infect. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Pompilio, A., Savini, V., Fiscarelli, E., Gherardi, G., and Di Bonaventura, G. (2020). Clonal diversity, biofilm formation, and antimicrobial resistance among Stenotrophomonas maltophilia strains from cystic fibrosis and non-cystic fibrosis patients. Antibiotics (Basel), 9.","DOI":"10.3390\/antibiotics9010015"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1007\/BF02877711","article-title":"Deflazacort: A glucocorticoid with few metabolic adverse effects but important immunosuppressive activity","volume":"24","author":"Luquin","year":"2007","journal-title":"Adv. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Parente, L. (2017). Deflazacort: Therapeutic index, relative potency and equivalent doses versus other corticosteroids. BMC Pharmacol. Toxicol., 18.","DOI":"10.1186\/s40360-016-0111-8"},{"key":"ref_25","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 Advances."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.idc.2004.04.012","article-title":"Pharmacodynamics of antimicrobial drugs","volume":"18","author":"Levison","year":"2004","journal-title":"Infect. Dis Clin. North. Am. Rev."},{"key":"ref_27","unstructured":"Clinical and Laboratory Standards Institute (2019). Performance Standards for Antimicrobial Susceptibility Testing, 29th Informational CLSI Supplement M100, Clinical and Laboratory Standards Institute."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"392058","DOI":"10.1155\/2013\/392058","article-title":"In vitro antibacterial and antibiofilm activities of chlorogenic acid against clinical isolates of Stenotrophomonas maltophilia including the trimethoprim\/sulfamethoxazole resistant strain","volume":"2013","author":"Karunanidhi","year":"2013","journal-title":"Biomed. Res. Int."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"9845075","DOI":"10.1155\/2018\/9845075","article-title":"Antibacterial and Antibiofilm Activities of Nonpolar Extracts of Allium stipitatum Regel. against Multidrug Resistant Bacteria","volume":"2018","author":"Karunanidhi","year":"2018","journal-title":"Biomed. Res. Int."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"617","DOI":"10.7150\/ijms.23924","article-title":"Anti-biofilm and Anti-Virulence Efficacy of Celastrol against Stenotrophomonas maltophilia","volume":"15","author":"Kim","year":"2018","journal-title":"Int. J. Med. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Pollini, S., Di Pilato, V., Landini, G., Di Maggio, T., Cannatelli, A., Sottotetti, S., Cariani, L., Aliberti, S., Blasi, F., and Sergio, F. (2018). In vitro activity of N-acetylcysteine against Stenotrophomonas maltophilia and Burkholderia cepacia complex grown in planktonic phase and biofilm. PLoS ONE., 13.","DOI":"10.1371\/journal.pone.0203941"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Pompilio, A., Crocetta, V., Scocchi, M., Pomponio, S., Di Vincenzo, V., Mardirossian, M., Gherardi, G., Fiscarelli, E., Dicuonzo, G., and Gennaro, R. (2012). Potential novel therapeutic strategies in cystic fibrosis: Antimicrobial and anti-biofilm activity of natural and designed \u03b1-helical peptides against Staphylococcus aureus, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. BMC Microbiol., 12.","DOI":"10.1186\/1471-2180-12-145"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Vidigal, P.G., M\u00fcsken, M., Becker, K.A., H\u00e4ussler, S., Wingender, J., Steinmann, E., Kehrmann, J., Gulbins, E., Buer, J., and Rath, P.M. (2014). Effects of green tea compound epigallocatechin-3-gallate against Stenotrophomonas maltophilia infection and biofilm. PLoS ONE., 9.","DOI":"10.1371\/journal.pone.0092876"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1111\/bcp.12356","article-title":"Targeting virulence not viability in the search for future antibacterials","volume":"79","author":"Heras","year":"2015","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"267","DOI":"10.4155\/fmc-2016-0227","article-title":"Disarming pathogens: Benefits and challenges of antimicrobials that target bacterial virulence instead of growth and viability","volume":"9","author":"Totsika","year":"2017","journal-title":"Future Med. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1128\/AEM.03408-14","article-title":"Genome-wide identification of genes necessary for biofilm formation by nosocomial pathogen Stenotrophomonas maltophilia reveals that orphan response regulator FsnR is a critical modulator","volume":"81","author":"Kang","year":"2015","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2444","DOI":"10.1128\/AEM.03951-15","article-title":"Systematic mutational analysis of histidine kinase genes in the nosocomial pathogen Stenotrophomonas maltophilia identifies BfmAK systemcontrol of biofilm development","volume":"82","author":"Zhenga","year":"2016","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Molloy, K., Smith, S.G., Cagney, G., Dillon, E.T., Greene, C.M., and McElvaney, N.G. (2019). Characterisation of the major extracellular proteases of Stenotrophomonas maltophilia and their effects on pulmonary antiproteases. Pathogens, 8.","DOI":"10.3390\/pathogens8030092"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3825","DOI":"10.1128\/IAI.00672-15","article-title":"Type II secretion-dependent degradative and cytotoxic activities mediated by Stenotrophomonas maltophilia serine proteases StmPr1 and StmPr2","volume":"83","author":"DuMont","year":"2015","journal-title":"Infect. Immun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e00544-17","DOI":"10.1128\/IAI.00544-17","article-title":"Stenotrophomonas maltophilia serine protease StmPr1 induces matrilysis, anoikis, and protease-activated receptor 2 activation in human lung epithelial cells","volume":"85","author":"DuMont","year":"2017","journal-title":"Infect. Immun."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Wu, C.J., Huang, Y.W., Lin, Y.T., Ning, H.C., and Yang, T.C. (2016). Inactivation of SmeSyRy two-component regulatory system inversely regulates the expression of SmeYZ and SmeDEF efflux pumps in Stenotrophomonas maltophilia. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0160943"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4067","DOI":"10.1128\/AAC.00372-15","article-title":"The SmeYZ efflux pump of Stenotrophomonas maltophilia contributes to drug resistance, virulence-related characteristics, and virulence in mice","volume":"59","author":"Lin","year":"2015","journal-title":"Antimicrob. Agents and Chemother."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0300-483X(95)03047-J","article-title":"Pharmacokinetics and receptor-mediated pharmacodynamics of corticosteroids","volume":"102","author":"Jusko","year":"1995","journal-title":"Toxicology"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Di Nocera, P.P., De Gregorio, E., and Rocco, F. (2013). GTAG- and CGTC-tagged palindromic DNA repeats in prokaryotes. BMC genomics, 14.","DOI":"10.1186\/1471-2164-14-522"},{"key":"ref_45","first-page":"185","article-title":"A giant family of short palindromic sequences in Stenotrophomonas maltophilia","volume":"308","author":"Rocco","year":"2010","journal-title":"FEMS Microbiol. Lett."},{"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","first-page":"44415","article-title":"Platinum nanoparticles inhibit bacteria proliferation and rescue zebrafish from bacterial infection","volume":"50","author":"Raman","year":"2016","journal-title":"RSC Adv."},{"key":"ref_48","unstructured":"Lorian, V. (2005). Antimicrobial combinations. Antibiotics in Laboratory Medicine, The Lippincott Williams & Wilkins Co.. [5th ed]."},{"key":"ref_49","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_50","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_51","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))","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\/3\/105\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:03:16Z","timestamp":1760173396000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/9\/3\/105"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,2]]},"references-count":51,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,3]]}},"alternative-id":["antibiotics9030105"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics9030105","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,2]]}}}