{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T06:59:04Z","timestamp":1793775544310,"version":"4.6.1"},"reference-count":118,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2020,10,29]],"date-time":"2020-10-29T00:00:00Z","timestamp":1603929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Bacteria are social organisms able to build complex structures, such as biofilms, that are highly organized surface-associated communities of microorganisms, encased within a self- produced extracellular matrix. Biofilm is commonly associated with many health problems since its formation increases resistance to antibiotics and antimicrobial agents, as in the case of Pseudomonas aeruginosa and Staphylococcus aureus, two human pathogens causing major concern. P. aeruginosa is responsible for severe nosocomial infections, the most frequent of which is ventilator-associated pneumonia, while S. aureus causes several problems, like skin infections, septic arthritis, and endocarditis, to name just a few. Literature data suggest that natural products from plants, bacteria, fungi, and marine organisms have proven to be effective as anti-biofilm agents, inhibiting the formation of the polymer matrix, suppressing cell adhesion and attachment, and decreasing the virulence factors\u2019 production, thereby blocking the quorum sensing network. Here, we focus on plant derived chemicals, and provide an updated literature review on the anti-biofilm properties of terpenes, flavonoids, alkaloids, and phenolic compounds. Moreover, whenever information is available, we also report the mechanisms of action.<\/jats:p>","DOI":"10.3390\/molecules25215024","type":"journal-article","created":{"date-parts":[[2020,10,29]],"date-time":"2020-10-29T23:06:12Z","timestamp":1604012772000},"page":"5024","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":136,"title":["Plant Derived Natural Products against Pseudomonas aeruginosa and Staphylococcus aureus: Antibiofilm Activity and Molecular Mechanisms"],"prefix":"10.3390","volume":"25","author":[{"given":"Francesca","family":"Guzzo","sequence":"first","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Ambientali Biologiche e Farmaceutiche\u2013DiSTABiF, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, via Vivaldi 43, I-81100 Caserta, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9614-0929","authenticated-orcid":false,"given":"Monica","family":"Scognamiglio","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Ambientali Biologiche e Farmaceutiche\u2013DiSTABiF, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, via Vivaldi 43, I-81100 Caserta, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9439-7074","authenticated-orcid":false,"given":"Antonio","family":"Fiorentino","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Ambientali Biologiche e Farmaceutiche\u2013DiSTABiF, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, via Vivaldi 43, I-81100 Caserta, Italy"},{"name":"Dipartimento di Biotecnologia Marina, Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9955-3179","authenticated-orcid":false,"given":"Elisabetta","family":"Buommino","sequence":"additional","affiliation":[{"name":"Dipartimento di Farmacia, Universit\u00e0 degli Studi di Napoli \u201cFederico II\u201d, Via Domenico Montesano 49, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6556-5462","authenticated-orcid":false,"given":"Brigida","family":"D\u2019Abrosca","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Ambientali Biologiche e Farmaceutiche\u2013DiSTABiF, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, via Vivaldi 43, I-81100 Caserta, Italy"},{"name":"Dipartimento di Biotecnologia Marina, Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/nrmicro.2015.8","article-title":"The biogeography of polymicrobial infection","volume":"14","author":"Stacy","year":"2016","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Kostakioti, M., Hadjifrangiskou, M., and Hultgren, S.J. (2013). Bacterial biofilms: Development, dispersal, and therapeutic strategies in the dawn of the postantibiotic era. Cold Spring Harb. Perspect. Med., 3.","DOI":"10.1101\/cshperspect.a010306"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Roilides, E., Simitsopoulou, M., Katragkou, A., and Walsh, T.J. (2015). How biofilms evade host defenses. Microbiol. Spectr., 3.","DOI":"10.1128\/microbiolspec.MB-0012-2014"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Trivedi, U., Parameswaran, S., Armstrong, A., Burgueno-Vega, D., Griswold, J., Dissanaike, S., and Rumbaugh, K.P. (2014). Prevalence of multiple antibiotic resistant infections in diabetic versus nondiabetic Wounds. J. Pathog., 173053.","DOI":"10.1155\/2014\/173053"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.ijmm.2015.11.004","article-title":"Antibiotic resistance in Pseudomonas aeruginosa and alternative therapeutic options","volume":"306","author":"Chatterjee","year":"2016","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.micpath.2016.10.028","article-title":"Staphylococcal chromosomal cassettes mec (SCCmec): A mobile genetic element in methicillin-resistant Staphylococcus aureus","volume":"101","author":"Liu","year":"2016","journal-title":"Microb. Pathog."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.mib.2020.02.003","article-title":"The social life of microbes in chronic infection","volume":"53","author":"Ibberson","year":"2020","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e00186-17","DOI":"10.1128\/mBio.00186-17","article-title":"Pseudomonas aeruginosa alginate overproduction promotes coexistence with Staphylococcus aureus in a model of cystic fibrosis respiratory infection","volume":"8","author":"Limoli","year":"2017","journal-title":"MBio"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1136\/thoraxjnl-2018-212616","article-title":"Help, hinder, hide and harm: What can we learn from the interactions between Pseudomonas aeruginosa and Staphylococcus aureus during respiratory infections?","volume":"74","author":"Limoli","year":"2019","journal-title":"Thorax"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Borges, A., Abreu, A.C., Dias, C., Saavedra, M.J., Borges, F., and Sim\u00f5es, M. (2016). New perspectives on the use of phytochemicals as an emergent strategy to Control Bacterial Infections Including Biofilms. Molecules, 21.","DOI":"10.3390\/molecules21070877"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1039\/C9MD00566H","article-title":"Virulence attenuating combination therapy: A potential multi-target synergy approach to treat Pseudomonas aeruginosa infections in cystic fibrosis patients","volume":"11","author":"Shaw","year":"2020","journal-title":"RSC Med. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4103\/JMAU.JMAU_10_18","article-title":"Anti-quorum sensing natural compounds","volume":"6","author":"Asfour","year":"2018","journal-title":"J. Microsc. Ultrastruct."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"7038","DOI":"10.1016\/j.bmc.2013.09.019","article-title":"Spectroscopic identification and anti-biofilm properties of polar metabolites from the medicinal plant Helichrysum italicum against Pseudomonas aeruginosa","volume":"21","author":"Buommino","year":"2013","journal-title":"Bioorg. Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4819","DOI":"10.1128\/IAI.05580-11","article-title":"Apple flavonoid phloretin inhibits Escherichia coli O157:H7 biofilm formation and ameliorates colon inflammation in rats","volume":"79","author":"Lee","year":"2011","journal-title":"Infect. Immun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2010","DOI":"10.3390\/md9102010","article-title":"Anti-Biofilm Compounds Derived from Marine Sponges","volume":"9","author":"Stowe","year":"2011","journal-title":"Mar. Drugs"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/1574-6941.12344","article-title":"Pseudomonas biofilms: Possibilities of their control","volume":"89","author":"Rezanka","year":"2014","journal-title":"FEMS Microbiol. Ecol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"789","DOI":"10.2174\/1385272821666170620110041","article-title":"A Review of Natural Products with Anti-biofilm Activity","volume":"22","author":"Song","year":"2018","journal-title":"Curr. Org. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1146\/annurev.cellbio.21.012704.131001","article-title":"Quorum sensing: Cell-to-cell communication in bacteria","volume":"21","author":"Waters","year":"2005","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_19","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_20","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s13020-019-0232-2","article-title":"Developing natural products as potential anti-biofilm agents","volume":"14","author":"Lu","year":"2019","journal-title":"Chin. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/ijos.2014.65","article-title":"Strategies for combating bacterial biofilm infections","volume":"7","author":"Wu","year":"2015","journal-title":"Int. J. Oral Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/nrmicro.2016.89","article-title":"Quorum sensing signal-response systems in gram-negative bacteria","volume":"14","author":"Papenfort","year":"2016","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1099\/jmm.0.001116","article-title":"The third quorum-sensing system of Pseudomonas aeruginosa: Pseudomonas quinolone signal and the enigmatic PqsE protein","volume":"69","year":"2020","journal-title":"J. Med. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.3389\/fmicb.2015.01174","article-title":"Quorum-sensing regulation in staphylococci-an overview","volume":"6","author":"Le","year":"2015","journal-title":"Front. Microbiol."},{"key":"ref_25","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_26","first-page":"228","article-title":"Pharmacological effects of hordenine","volume":"102","author":"Hapke","year":"1995","journal-title":"Dtsch. Tierarztl. Wochenschr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1021\/acs.jafc.7b05035","article-title":"Hordenine: A Novel Quorum Sensing Inhibitor and Anti-biofilm Agent against Pseudomonas aeruginosa","volume":"66","author":"Zhou","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3061","DOI":"10.1128\/AEM.02677-10","article-title":"The swarming motility of Pseudomonas aeruginosa is blocked by cranberry proanthocyanidins and other tannin-containing materials","volume":"77","author":"Tufenkji","year":"2011","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1136\/thx.2009.133082","article-title":"Quorum sensing-dependent virulence during Pseudomonas aeruginosa colonisation and pneumonia in mechanically ventilated patients","volume":"65","author":"Guanella","year":"2010","journal-title":"Thorax"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1007\/s00203-019-01775-0","article-title":"Inhibition of biofilm formation of Pseudomonas aeruginosa by caffeine: A potential approach for sustainable management of biofilm","volume":"202","author":"Chakraborty","year":"2020","journal-title":"Arch. Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1111\/j.1574-6968.2012.02500.x","article-title":"7-fluoroindole as an antivirulence compound against Pseudomonas aeruginosa","volume":"329","author":"Lee","year":"2012","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1146\/annurev.bi.53.070184.003533","article-title":"Polyamines","volume":"53","author":"Tabor","year":"1984","journal-title":"Ann. Rev. Biochem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1002\/mbo3.338","article-title":"Effects of norspermidine on Pseudomonas aeruginosa biofilm formation and eradication","volume":"5","author":"Qu","year":"2016","journal-title":"Microbiologyopen"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.fitote.2017.04.006","article-title":"Natural isothiocyanates express antimicrobial activity against developing and mature biofilms of Pseudomonas aeruginosa","volume":"119","author":"Kaiser","year":"2017","journal-title":"Fitoterapia"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2314","DOI":"10.1128\/AAC.05919-11","article-title":"Ajoene, a Sulfur-Rich Molecule from Garlic, Inhibits Genes Controlled by Quorum Sensing","volume":"56","author":"Jakobsen","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"127","DOI":"10.2217\/fmb-2019-0204","article-title":"Terpinen-4-ol attenuates quorum sensing regulated virulence factors and biofilm formation in Pseudomonas aeruginosa","volume":"15","author":"Bose","year":"2020","journal-title":"Future Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"103","DOI":"10.4103\/0973-7847.79105","article-title":"Feverfew (Tanacetum parthenium L.): A systematic review","volume":"5","author":"Pareek","year":"2011","journal-title":"Pharmacogn. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.lfs.2018.03.013","article-title":"Exploring the impact of parthenolide as anti-quorum sensing and anti-biofilm agent against Pseudomonas aeruginosa","volume":"199","author":"Kalia","year":"2018","journal-title":"Life Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.bmc.2019.115229","article-title":"Optimized plant compound with potent anti-biofilm activity across gram-negative","volume":"28","author":"Lawrence","year":"2020","journal-title":"Bioorg. Med. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"103901","DOI":"10.1016\/j.micpath.2019.103901","article-title":"The anti-biofilm potential of triterpenoids isolated from Sarcochlamys pulcherrima (Roxb.) Gaud","volume":"139","author":"Ghosh","year":"2020","journal-title":"Microb. Pathog."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e1700165","DOI":"10.1002\/cbdv.201700165","article-title":"Exploration of Phytoconstituents from Mussaenda roxburghii and Studies of their Antibiofilm Effect","volume":"14","author":"Ghosh","year":"2017","journal-title":"Chem. Biodivers."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.micpath.2018.03.012","article-title":"Attenuation of quorum sensing controlled virulence factors and biofilm formation in Pseudomonas aeruginosa by pentacyclic triterpenes, betulin and betulinic acid","volume":"118","author":"Rajkumari","year":"2018","journal-title":"Microb. Pathog."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1139\/cjm-2016-0365","article-title":"Effect of Bacoside A on growth and biofilm formation by Staphylococcus aureus and Pseudomonas aeruginosa","volume":"63","author":"Parai","year":"2017","journal-title":"Can. J. Microbiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1021\/acs.jnatprod.8b00970","article-title":"Antibacterial and Antibiofilm Activity of Flavonoid and Saponin Derivatives from Atriplex tatarica against Pseudomonas aeruginosa","volume":"82","year":"2019","journal-title":"J. Nat. Prod."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.micpath.2016.07.001","article-title":"Alternative to antibiotics against Pseudomonas aeruginosa: Effects of Glycyrrhiza glabra on membrane permeability and inhibition of efflux activity and biofilm formation in Pseudomonas aeruginosa and its in vitro time-kill activity","volume":"98","author":"Chakotiya","year":"2016","journal-title":"Microb. Pathog."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Mozirandi, W., Tagwireyi, D., and Mukanganyama, S. (2019). Evaluation of antimicrobial activity of chondrillasterol isolated from Vernonia adoensis (Asteraceae). BMC Complement. Altern. Med., 249.","DOI":"10.1186\/s12906-019-2657-7"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3015","DOI":"10.1128\/AAC.00575-10","article-title":"Synergistic effect of 14-alpha-lipoyl andrographolide and various antibiotics on the formation of biofilms and production of exopolysaccharide and pyocyanin by Pseudomonas aeruginosa","volume":"55","author":"Zeng","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1124\/pr.115.010843","article-title":"Botanicals and their bioactive phytochemicals for women\u2019s health","volume":"68","author":"Dietz","year":"2016","journal-title":"Pharmacol. Rev."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Kuang, Z., Hao, Y., Walling, B.E., Jeffries, J.L., Ohman, D.E., and Gee, W.L. (2011). Pseudomonas aeruginosa elastase provides an escape from phagocytosis by degrading the pulmonary surfactant protein-A. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0027091"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"483","DOI":"10.4103\/0250-474X.98981","article-title":"A review on the taxonomy, ethnobotany, chemistry and pharmacology of Oroxylum indicum Vent","volume":"73","author":"Chaudhary","year":"2011","journal-title":"Indian J. Pharm Sci."},{"key":"ref_51","first-page":"987326","article-title":"Chinese medicine injection Shuanghuanglian for treatment of acute upper respiratory tract infection: A systematic review of randomized controlled trials","volume":"2013","author":"Zhang","year":"2013","journal-title":"J. Evid. Based Complement. Altern. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"183","DOI":"10.2147\/DDDT.S97221","article-title":"Baicalein attenuates the quorum sensing-controlled virulence factors of Pseudomonas aeruginosa and relieves the inflammatory response in P. aeruginosa-infected macrophages by downregulating the MAPK and NF\u03baB signal-transduction pathways","volume":"10","author":"Luo","year":"2016","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2120","DOI":"10.1099\/mic.0.049338-0","article-title":"The flavanone naringenin reduces the production of quorum sensing-controlled virulence factors in Pseudomonas aeruginosa PAO1","volume":"157","author":"Vandeputte","year":"2011","journal-title":"Microbiology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1128\/AEM.01059-09","article-title":"Identification of catechin as one of the flavonoids from Combretum albiflorum bark extract that reduces the production of quorum-sensing-controlled virulence factors in Pseudomonas aeruginosa PAO1","volume":"76","author":"Vandeputte","year":"2010","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"151410","DOI":"10.1016\/j.ijmm.2020.151410","article-title":"Naringin sensitizes the antibiofilm effect of ciprofloxacin and tetracycline against Pseudomonas aeruginosa biofilm","volume":"310","author":"Dey","year":"2020","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.bioorg.2019.03.050","article-title":"Inhibition of biofilm formation, quorum sensing activity and molecular docking study of isolated 3, 5, 7-Trihydroxyflavone from Alstonia scholaris leaf against P. aeruginosa","volume":"87","author":"Abinaya","year":"2019","journal-title":"Bioorg. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"23347","DOI":"10.1038\/srep23347","article-title":"Attenuation of Pseudomonas aeruginosa biofilm formation by Vitexin: A combinatorial study with azithromycin and gentamicin","volume":"6","author":"Das","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1021\/acssuschemeng.6b01806","article-title":"Intrinsic Hydrophobic Antibacterial Thin Film from renewable Resources: Application in the Development of Anti-Biofilm Urinary Catheters","volume":"5","author":"Lalitha","year":"2017","journal-title":"Acs Sustain. Chem. Eng."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1021\/acsabm.9b00850","article-title":"Co-delivery of Diverse Therapeutic Compounds Using PEG-PLGA Nanoparticle Cargo against Drug-Resistant Bacteria: An Improved Anti-biofilm Strategy","volume":"3","author":"Deepika","year":"2020","journal-title":"ACS Appl. Bio Mater."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.22207\/JPAM.12.4.35","article-title":"Methanolic Extract of Plectranthus tenuiflorus Attenuates Quorum Sensing Mediated Virulence and Biofilm Formation in Pseudomonas aeruginosa PAO1","volume":"12","author":"Hnamte","year":"2018","journal-title":"J. Pure Appl. Microbiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.jmii.2014.03.012","article-title":"Anti-quorum sensing activity of flavonoid-rich fraction from Centella asiatica L. against Pseudomonas aeruginosa PAO1","volume":"49","author":"Vasavi","year":"2016","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"ref_62","first-page":"186864","article-title":"A review on antibacterial, antiviral, and antifungal activity of curcumin","volume":"2014","author":"Moghadamtousi","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1021\/jf072591j","article-title":"Curcumin, a known phenolic from Curcuma longa, attenuates the virulence of Pseudomonas aeruginosa PAO1 in whole plant and animal pathogenicity models","volume":"56","author":"Rudrappa","year":"2008","journal-title":"J. Agric Food Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3399","DOI":"10.1021\/acs.molpharmaceut.9b00179","article-title":"ZnO\/Curcumin Nanocomposites for Enhanced Inhibition of Pseudomonas aeruginosa Virulence via LasR-RhlR Quorum Sensing Systems","volume":"16","author":"Das","year":"2019","journal-title":"Mol. Pharm."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1111\/jam.13476","article-title":"Potentiation of antibiotic against Pseudomonas aeruginosa biofilm: A study with plumbagin and gentamicin","volume":"123","author":"Gupta","year":"2017","journal-title":"J. Appl. Microbiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"7838","DOI":"10.1021\/bi800730q","article-title":"The natural naphthoquinone plumbagin exhibits antiproliferative activity and disrupts the microtubule network through tubulin binding","volume":"47","author":"Acharya","year":"2008","journal-title":"Biochemistry"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1007\/s10529-018-2557-9","article-title":"Cinnamic acid attenuates quorum sensing associated virulence factors and biofilm formation in Pseudomonas aeruginosa PAO1","volume":"40","author":"Rajkumari","year":"2018","journal-title":"Biotechnol. Lett."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.3389\/fmicb.2020.01068","article-title":"Membrane-interactive compounds from Pistacia lentiscus L. thwart Pseudomonas aeruginosa virulence","volume":"11","author":"Tahrioui","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1007\/s10529-012-1126-x","article-title":"Eugenol inhibits quorum sensing at sub-inhibitory concentrations","volume":"35","author":"Zhou","year":"2013","journal-title":"Biotechnol. Lett."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1111\/apm.12083","article-title":"Effect of plant phenolic compounds on biofilm formation by Pseudomonas aeruginosa","volume":"121","author":"Plyuta","year":"2013","journal-title":"APMIS"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1080\/08927014.2012.706751","article-title":"The activity of ferulic and gallic acids in biofilm prevention and control of pathogenic bacteria","volume":"28","author":"Borges","year":"2012","journal-title":"Biofouling"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3521","DOI":"10.1007\/s00253-019-09618-0","article-title":"Natural quorum sensing inhibitors effectively down-regulate gene expression of Pseudomonas aeruginosa virulence factors","volume":"103","author":"Ahmed","year":"2019","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"8656","DOI":"10.1038\/srep08656","article-title":"6-Gingerol reduces Pseudomonas aeruginosa biofilm formation and virulence via quorum sensing inhibition","volume":"5","author":"Kim","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.fitote.2013.06.017","article-title":"Zingerone inhibit biofilm formation and improve antibiofilm efficacy of ciprofloxacin against Pseudomonas aeruginosa PAO1","volume":"90","author":"Kumar","year":"2013","journal-title":"Fitoterapia"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.fitote.2015.02.002","article-title":"Zingerone silences quorum sensing and attenuates virulence of Pseudomonas aeruginosa","volume":"102","author":"Kumar","year":"2015","journal-title":"Fitoterapia"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Ulrey, R.K., Barksdale, S.M., Zhou, W., and van Hoek, M.L. (2014). Cranberry proanthocyanidins have anti-biofilm properties against Pseudomonas aeruginosa. BMC Complement. Altern. Med., 14.","DOI":"10.1186\/1472-6882-14-499"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e00026-19","DOI":"10.1128\/MMBR.00026-19","article-title":"Staphylococcal Biofilm Development: Structure, Regulation, and Treatment Strategies","volume":"84","author":"Schilcher","year":"2020","journal-title":"Microbiol. Mol. Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"13195","DOI":"10.1021\/acs.jafc.9b05595","article-title":"Natural Products That Target Virulence factors in Antibiotic-Resistant Staphylococcus aureus","volume":"67","author":"Wu","year":"2019","journal-title":"J. Agric. Food Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.micpath.2018.03.006","article-title":"Assessment of the antibiofilm and antiquorum sensing activities of Eucalyptus globulus essential oil and its main component 1,8-cineole against methicillin-resistant Staphylococcus aureus strains","volume":"118","author":"Merghni","year":"2018","journal-title":"Microb. Pathog."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Burt, S.A., Ojo-Fakunle, V.T., Woertman, J., and Veldhuizen, E.J. (2014). The Natural Antimicrobial Carvacrol Inhibits Quorum Sensing in Chromobacterium violaceum and Reduces Bacterial Biofilm Formation at Sub-Lethal Concentrations. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0093414"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1007\/s10482-014-0364-4","article-title":"Anti-virulence potential of eugenyl acetate against pathogenic bacteria of medical importance","volume":"107","author":"Musthafa","year":"2015","journal-title":"Antonie Leeuwenhoek."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Farha, A.K., Yang, Q.Q., Kim, G., Zhang, D., Mavumengwana, V., Habimana, O., Li, H.B., Corke, H., and Gana, R.Y. (2020). Inhibition of multidrug-resistant foodborne Staphylococcus aureus biofilms by a natural terpenoid (+)-nootkatone and related molecular mechanism. Food Control., 107154.","DOI":"10.1016\/j.foodcont.2020.107154"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1055\/s-2007-967179","article-title":"Salvipisone and aethiopinone from Salvia sclarea hairy roots modulate staphylococcal antibiotic resistance and express anti-biofilm activity","volume":"73","author":"Walencka","year":"2007","journal-title":"Planta Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s12223-016-0485-4","article-title":"Activity of novel inhibitors of Staphylococcus aureus biofilms","volume":"62","author":"Woo","year":"2017","journal-title":"Folia Microbiol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep05467","article-title":"RNA-Seq-based transcriptome analysis of methicillin-resistant Staphylococcus aureus biofilm inhibition by ursolic acid and resveratrol","volume":"4","author":"Qin","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1016\/j.bmc.2011.11.052","article-title":"Bacterial biofilm formation inhibitory activity revealed for plant derived natural compounds","volume":"20","author":"Artini","year":"2012","journal-title":"Bioorg. Med. Chem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.4014\/jmb.1202.02017","article-title":"alpha-Cyperone Alleviates Lung Cell Injury Caused by Staphylococcus aureus via Attenuation of alpha-Hemolysin Expression","volume":"22","author":"Luo","year":"2012","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Chen, Y., Liu, T., Wang, K., Hou, C., Cai, S., Huang, Y., Du, Z., Huang, H., Kong, J., and Chen, Y. (2016). Baicalein Inhibits Staphylococcus aureus Biofilm Formation and the Quorum Sensing System In Vitro. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0153468"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2823","DOI":"10.1038\/s41598-017-02712-1","article-title":"Myricetin protects Galleria mellonella against Staphylococcus aureus infection and inhibits multiple virulence factors","volume":"7","author":"Silva","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_90","first-page":"131","article-title":"Quercetin attenuates Staphylococcus aureus virulence by reducing alpha-toxin secretion","volume":"50","author":"Lopez","year":"2018","journal-title":"Rev. Argent. Microbiol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1111\/j.1574-6968.2010.02183.x","article-title":"Subinhibitory concentrations of farrerol reduce alpha-toxin expression in Staphylococcus aureus","volume":"315","author":"Qiu","year":"2011","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"596","DOI":"10.4014\/jmb.1507.07091","article-title":"Isorhamnetin Attenuates Staphylococcus aureus-Induced Lung Cell Injury by Inhibiting Alpha-Hemolysin Expression","volume":"26","author":"Jiang","year":"2016","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"6697","DOI":"10.1007\/s00253-017-8417-z","article-title":"Lysionotin attenuates Staphylococcus aureus pathogenicity by inhibiting alpha-toxin expression","volume":"101","author":"Teng","year":"2017","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/s10482-015-0491-6","article-title":"Diosmetin inhibits the expression of alpha-hemolysin in Staphylococcus aureus","volume":"108","author":"Liu","year":"2015","journal-title":"Antonie Leeuwenhoek."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1111\/1574-6968.12040","article-title":"Apigenin alleviates the symptoms of Staphylococcus aureus pneumonia by inhibiting the production of alpha-hemolysin","volume":"338","author":"Dong","year":"2013","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.micpath.2017.12.054","article-title":"Epigallocatechin gallate can attenuate human alveolar epithelial cell injury induced by alpha-haemolysin","volume":"115","author":"Zhou","year":"2018","journal-title":"Microb. Pathog."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1093\/infdis\/jis336","article-title":"Baicalin Protects Mice From Staphylococcus aureus Pneumonia Via Inhibition of the Cytolytic Activity of alpha-Hemolysin","volume":"206","author":"Qiu","year":"2012","journal-title":"J. Infect. Dis."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Dong, J., Qiu, J.Z., Zhang, Y., Lu, C.J., Dai, X.H., Wang, J.F., Li, H.G., Wang, X., Tan, W., and Luo, M.J. (2013). Oroxylin A Inhibits Hemolysis via Hindering the Self-Assembly of alpha-Hemolysin Heptameric Transmembrane Pore. PLoS Comput. Biol., 9.","DOI":"10.1371\/journal.pcbi.1002869"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s11274-016-2129-x","article-title":"Dracorhodin Perochlorate attenuates Staphylococcus aureus USA300 virulence by decreasing alpha-toxin expression","volume":"33","author":"Liu","year":"2017","journal-title":"World J. Microbiol. Biotechnol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1055\/s-0032-1328068","article-title":"Silibinin In Vitro Protects A549 Cells from Staphylococcus aureus-Mediated Injury and In Vivo Alleviates the Lung Injury of Staphylococcal Pneumonia","volume":"79","author":"Wang","year":"2013","journal-title":"Planta Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.foodcont.2017.03.004","article-title":"Rutin inhibits mono and multi-species biofilm formation by foodborne drug resistant Escherichia coli and Staphylococcus aureus","volume":"79","author":"Husain","year":"2017","journal-title":"Food Control."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1021\/np5004092","article-title":"Teucrium polium phenylethanol and iridoid glycoside characterization and flavonoid inhibition of biofilm-forming Staphylococcus aureus","volume":"78","author":"Elmasri","year":"2015","journal-title":"J. Nat. Prod."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.3389\/fmicb.2017.02263","article-title":"Kaempferol Inhibits the Primary Attachment Phase of Biofilm Formation in Staphylococcus aureus","volume":"8","author":"Ming","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1007\/s11274-015-1879-1","article-title":"Phloretin derived from apple can reduce alpha-hemolysin expression in methicillin-resistant Staphylococcus aureus USA300","volume":"31","author":"Zhou","year":"2015","journal-title":"World J. Microbiol. Biotechnol."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Liu, S., Liu, B.W., Luo, Z.Q., Qiu, J.M., Zhou, X.A., Li, G., Zhang, B., Deng, X.M., Yang, Z.G., and Wang, J.F. (2017). The combination of osthole with baicalin protects mice from Staphylococcus aureus pneumonia. World J. Microbiol. Biotechnol.","DOI":"10.1007\/s11274-016-2162-9"},{"key":"ref_106","first-page":"1","article-title":"Chalcone Attenuates Staphylococcus aureus Virulence by Targeting Sortase A and Alpha-Hemolysin","volume":"8","author":"Zhang","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_107","first-page":"1","article-title":"Subinhibitory concentrations of resveratrol reduce alpha-hemolysin production in Staphylococcus aureus isolates by down-regulating saeRS","volume":"7","author":"Duan","year":"2018","journal-title":"Emerg. Microbes Infect."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"28254","DOI":"10.1038\/srep28254","article-title":"Curcumin protects mice from Staphylococcus aureus pneumonia by interfering with the self-assembly process of alpha-hemolysin","volume":"6","author":"Wang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_109","first-page":"2108","article-title":"Preliminary study on the effect of brazilin on biofilms of Staphylococcus aureus","volume":"16","author":"Peng","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"6551","DOI":"10.1002\/anie.201601973","article-title":"Hamamelitannin Analogues that Modulate Quorum Sensing as Potentiators of Antibiotics against Staphylococcus aureus","volume":"55","author":"Vermote","year":"2016","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1124\/mol.107.044164","article-title":"Discovery of a quorum-sensing inhibitor of drug resistant staphylococcal infections by structure-based virtual screening","volume":"73","author":"Kiran","year":"2008","journal-title":"Mol. Pharmacol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"fnw253","DOI":"10.1093\/femsle\/fnw253","article-title":"Subinhibitory concentrations of punicalagin reduces expression of virulence-related exoproteins by Staphylococcus aureus","volume":"363","author":"Mun","year":"2016","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1089\/fpd.2016.2226","article-title":"Antimicrobial Activity of Punicalagin Against Staphylococcus aureus and Its Effect on Biofilm Formation","volume":"14","author":"Xu","year":"2017","journal-title":"Foodborne Pathog. Dis."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2225","DOI":"10.1080\/14786419.2017.1366485","article-title":"Antimicrobial and anti-biofilm activity of tannic acid against Staphylococcus aureus","volume":"32","author":"Dong","year":"2018","journal-title":"Nat. Prod. Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1128\/AAC.00843-10","article-title":"Inhibitory effects of 1, 2, 3, 4, 6-penta-O-galloyl-\u03b2-D-glucopyranose on biofilm formation by Staphylococcus aureus","volume":"55","author":"Lin","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_116","first-page":"21","article-title":"Antimicrobial and anti-biofilm properties of novel synthetic lignan-like compounds","volume":"42","author":"Vollaro","year":"2019","journal-title":"New Microbiol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1111\/cbdd.13497","article-title":"Proteoliposome-based model for screening inhibitors targeting histidine kinase AgrC","volume":"93","author":"Zhang","year":"2019","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1099\/jmm.0.033092-0","article-title":"Rhodomyrtus tomentosa (Aiton) Hassk. ethanol extract and rhodomyrtone: A potential strategy for the treatment of biofilm-forming staphylococci","volume":"60","author":"Saising","year":"2011","journal-title":"J. Med. Microbiol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/21\/5024\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:26:36Z","timestamp":1760178396000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/21\/5024"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,29]]},"references-count":118,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["molecules25215024"],"URL":"https:\/\/doi.org\/10.3390\/molecules25215024","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,29]]}}}