{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:10:45Z","timestamp":1790115045671,"version":"4.0.1"},"reference-count":67,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,1,10]],"date-time":"2020-01-10T00:00:00Z","timestamp":1578614400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31702284"],"award-info":[{"award-number":["31702284"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Double subject construction plan of Sichuan Agriculture University","award":["03571444"],"award-info":[{"award-number":["03571444"]}]},{"DOI":"10.13039\/501100012438","name":"Sichuan Veterinary Medicine and Drug Innovation Group of China Agricultural Research System","doi-asserted-by":"publisher","award":["CARS-SVDIP"],"award-info":[{"award-number":["CARS-SVDIP"]}],"id":[{"id":"10.13039\/501100012438","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Methicillin-resistant Staphylococcus aureus (MRSA) is a common human pathogen that causes several difficult-to-treat infections, including biofilm-associated infections. The biofilm-forming ability of S. aureus plays a pivotal role in its resistance to most currently available antibiotics, including vancomycin, which is the first-choice drug for treating MRSA infections. In this study, the ability of thymol (a monoterpenoid phenol isolated from plants) to inhibit biofilm formation and to eliminate mature biofilms, was assessed. We found that thymol could inhibit biofilm formation and remove mature biofilms by inhibiting the production of polysaccharide intracellular adhesin (PIA) and the release of extracellular DNA (eDNA). However, cotreatment with thymol and vancomycin was more effective at eliminating MRSA biofilms, in a mouse infection model, than monotherapy with vancomycin. Comparative histopathological analyses revealed that thymol reduced the pathological changes and inflammatory responses in the wounds. Assessments of white blood cell counts and serum TNF-\u03b1 and IL-6 levels showed reduced inflammation and an increased immune response following treatment with thymol and vancomycin. These results indicate that combinatorial treatment with thymol and vancomycin has the potential to serve as a more effective therapy for MRSA biofilm-associated infections than vancomycin monotherapy.<\/jats:p>","DOI":"10.3390\/microorganisms8010099","type":"journal-article","created":{"date-parts":[[2020,1,10]],"date-time":"2020-01-10T10:20:29Z","timestamp":1578651629000},"page":"99","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Thymol Inhibits Biofilm Formation, Eliminates Pre-Existing Biofilms, and Enhances Clearance of Methicillin-Resistant Staphylococcus aureus (MRSA) in a Mouse Peritoneal Implant Infection Model"],"prefix":"10.3390","volume":"8","author":[{"given":"Zhongwei","family":"Yuan","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Sichuan Agriculture University, Huimin Lu 211, Wenjiang 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyun","family":"Dai","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Sichuan Agriculture University, Huimin Lu 211, Wenjiang 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Ouyang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Sichuan Agriculture University, Huimin Lu 211, Wenjiang 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tayyab","family":"Rehman","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Sichuan Agriculture University, Huimin Lu 211, Wenjiang 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sajjad","family":"Hussain","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Sichuan Agriculture University, Huimin Lu 211, Wenjiang 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Sichuan Agriculture University, Huimin Lu 211, Wenjiang 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongqiong","family":"Yin","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Sichuan Agriculture University, Huimin Lu 211, Wenjiang 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hualin","family":"Fu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Sichuan Agriculture University, Huimin Lu 211, Wenjiang 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juchun","family":"Lin","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Sichuan Agriculture University, Huimin Lu 211, Wenjiang 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changliang","family":"He","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Sichuan Agriculture University, Huimin Lu 211, Wenjiang 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Lv","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Sichuan Agriculture University, Huimin Lu 211, Wenjiang 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxia","family":"Liang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Sichuan Agriculture University, Huimin Lu 211, Wenjiang 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Shu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Sichuan Agriculture University, Huimin Lu 211, Wenjiang 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Song","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Sichuan Agriculture University, Huimin Lu 211, Wenjiang 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixia","family":"Li","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Sichuan Agriculture University, Huimin Lu 211, Wenjiang 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanfeng","family":"Zou","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Sichuan Agriculture University, Huimin Lu 211, Wenjiang 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lizi","family":"Yin","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Sichuan Agriculture University, Huimin Lu 211, Wenjiang 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1056\/NEJM199808203390806","article-title":"Staphylococcus aureus infections","volume":"339","author":"Lowy","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/nrmicro3161","article-title":"Adhesion, invasion, and evasion: The many functions of the surface proteins of Staphylococcus aureus","volume":"12","author":"Foster","year":"2014","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"404","DOI":"10.3390\/pathogens3020404","article-title":"Antibiofilm effect of octenidine hydrochloride on Staphylococcus aureus, MRSA and VRSA","volume":"3","author":"Amalaradjou","year":"2014","journal-title":"Pathogens"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S20","DOI":"10.1093\/cid\/cit614","article-title":"Methicillin-resistant Staphylococcus aureus therapy: Past, present, and future","volume":"58","author":"Rodvold","year":"2014","journal-title":"Clin. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"s3","DOI":"10.1089\/sur.2008.066.supp","article-title":"Complicated skin and soft tissue infections caused by methicillin-resistant Staphylococcus aureus: Epidemiology, risk factors, and presentation","volume":"9","author":"Dryden","year":"2008","journal-title":"Surg. Infect."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1001\/jama.298.15.1763","article-title":"Active Bacterial Core surveillance (ABCs) MRSA Investigators. Invasive methicillin-resistant Staphylococcus aureus infections in the United States","volume":"298","author":"Klevens","year":"2007","journal-title":"JAMA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1002\/jor.23656","article-title":"Bacteria antibiotic resistance: New challenges and opportunities for implant-associated orthopedic infections","volume":"36","author":"Li","year":"2018","journal-title":"J. Orthop. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.cmi.2015.12.002","article-title":"The negative impact of antibiotic resistance","volume":"22","author":"Friedman","year":"2016","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1111\/j.1749-6632.2011.06281.x","article-title":"New approaches for treating staphylococcal biofilm infections","volume":"1241","author":"Kiedrowski","year":"2011","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_10","first-page":"204","article-title":"The challenge of treating biofilm-associated bacterial infections","volume":"82","author":"Patel","year":"2007","journal-title":"Clin. Pharm."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.micpath.2018.07.002","article-title":"Vision for medicine: Staphylococcus aureus biofilm war and unlocking key\u2019s for anti-biofilm drug development","volume":"123","author":"Mohammed","year":"2018","journal-title":"Microb. Pathog."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1111\/2049-632X.12141","article-title":"Anti-biofilm agents: Recent breakthrough against multi-drug resistant Staphylococcus aureus","volume":"70","author":"Chung","year":"2014","journal-title":"Pathog. Dis."},{"key":"ref_13","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_14","doi-asserted-by":"crossref","first-page":"3835","DOI":"10.1128\/JB.00167-08","article-title":"A novel Staphylococcus aureus biofilm phenotype mediated by the fibronectin-binding proteins, FnBPA and FnBPB","volume":"190","author":"Pozzi","year":"2008","journal-title":"J. Bacteriol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.tim.2011.06.004","article-title":"Staphylococcal biofilm disassembly","volume":"19","author":"Boles","year":"2011","journal-title":"Trends Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/s41522-017-0026-1","article-title":"Norgestimate inhibits staphylococcal biofilm formation and resensitizes methicillin-resistant Staphylococcus aureus to \u03b2-lactam antibiotics","volume":"3","author":"Yoshii","year":"2017","journal-title":"NPJ Biofilms Microbiomes"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5418","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_18","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1093\/jac\/dkq257","article-title":"Penetration of antibiotics through Staphylococcus aureus and Staphylococcus epidermidis biofilms","volume":"65","author":"Singh","year":"2010","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"22296","DOI":"10.3390\/ijms151222296","article-title":"Chitosan improves anti-biofilm efficacy of gentamicin through facilitating antibiotic penetration","volume":"15","author":"Mu","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.micres.2016.12.003","article-title":"Phytochemicals for human disease: An update on plant-derived compounds antibacterial activity","volume":"196","author":"Barbieri","year":"2017","journal-title":"Microbiol. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1007\/s13205-017-0848-9","article-title":"Plant-derived antimicrobials to fight against multi-drug-resistant human pathogens","volume":"7","author":"Subramani","year":"2017","journal-title":"3 Biotech"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Luna, A., Lema-Alba, R.C., Dambolena, J.S., Zygadlo, J.A., Labaque, M.C., and Marin, R.H. (2017). Thymol as natural antioxidant additive for poultry feed: Oxidative stability improvement. Poult. Sci., 96.","DOI":"10.3382\/ps\/pex158"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.foodchem.2016.04.111","article-title":"Antibacterial and antifungal activities of thymol: A brief review of the literature","volume":"210","author":"Marchese","year":"2016","journal-title":"Food Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"8382","DOI":"10.1021\/acs.jafc.9b03517","article-title":"Thymol mediates bactericidal activity against Staphylococcus aureus by targeting an aldo-keto reductase and consequent depletion of NADPH","volume":"67","author":"Zhou","year":"2019","journal-title":"J Agric. Food Chem."},{"key":"ref_25","first-page":"18","article-title":"Antibacterial mechanism of thymol on methicillin-resistant Staphylococcus aureus (MRSA)","volume":"6","author":"Yuan","year":"2018","journal-title":"J. South. China Agric. Univ."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fcimb.2015.00001","article-title":"Methicillin resistance and the biofilm phenotype in Staphylococcus aureus","volume":"5","author":"McCarthy","year":"2015","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1099\/0022-1317-50-7-582","article-title":"Staphylococcus epidermidis biofilms: Importance and implications","volume":"50","author":"Humphreys","year":"2001","journal-title":"J. Med. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1128\/JCM.00651-13","article-title":"Molecular characterization of endocarditis-associated Staphylococcus Aureus","volume":"51","author":"Nethercott","year":"2013","journal-title":"J. Clin. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6671","DOI":"10.1007\/s00253-017-8403-5","article-title":"Aloe-emodin inhibits Staphylococcus aureus biofilms and extracellular protein production at the initial adhesion stage of biofilm development","volume":"101","author":"Xiang","year":"2017","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_30","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_31","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/j.pnsc.2008.04.001","article-title":"Bacterial adhesion and biofilms on surfaces","volume":"18","author":"Garrett","year":"2008","journal-title":"Prog. Nat. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1080\/1040841X.2017.1282941","article-title":"The role of biofilms in persistent infections and factors involved in ica-independent biofilm development and gene regulation in Staphylococcus aureus","volume":"43","author":"Figueiredo","year":"2017","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1016\/j.chembiol.2012.10.022","article-title":"Molecular basis of in vivo biofilm formation by bacterial pathogens","volume":"19","author":"Joo","year":"2012","journal-title":"Chem. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"38","DOI":"10.3389\/fcimb.2012.00038","article-title":"Genetic regulation of the intercellular adhesion locus in staphylococci","volume":"2","author":"Cue","year":"2012","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3480","DOI":"10.1099\/mic.0.2007\/016014-0","article-title":"Agr RNAIII divergently regulates glucose-induced biofilm formation in clinical isolates of Staphylococcus aureus","volume":"154","author":"Coelho","year":"2008","journal-title":"Microbiology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4665","DOI":"10.1128\/JB.186.14.4665-4684.2004","article-title":"Global gene expression in Staphylococcus aureus biofilms","volume":"186","author":"Beenken","year":"2004","journal-title":"J. Bacteriol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.1128\/JB.187.7.2348-2356.2005","article-title":"SarA is an essential positive regulator of Staphylococcus epidermidis biofilm development","volume":"187","author":"Tormo","year":"2005","journal-title":"J. Bacteriol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1046\/j.1365-2958.2003.03493.x","article-title":"SarA and not sigmaB is essential for biofilm development by Staphylococcus aureus","volume":"48","author":"Valle","year":"2003","journal-title":"Mol. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"171","DOI":"10.3389\/fcimb.2014.00171","article-title":"Protein-based biofilm matrices in Staphylococci","volume":"4","author":"Speziale","year":"2014","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1128\/IAI.00364-10","article-title":"Essential role for the major autolysin in the fibronectin-binding protein-mediated Staphylococcus aureus biofilm phenotype","volume":"79","author":"Houston","year":"2011","journal-title":"Infect. Immun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.copbio.2014.12.002","article-title":"Extracellular DNA as a target for biofilm control","volume":"33","author":"Okshevsky","year":"2015","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/ja.2011.113","article-title":"Recombinant human DNase I decreases biofilm and increases antimicrobial susceptibility in staphylococci","volume":"65","author":"Kaplan","year":"2012","journal-title":"J. Antibiot."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.micpath.2015.02.007","article-title":"Drug resistance of bacterial dental biofilm and the potential use of natural compounds as alternative for prevention and treatment","volume":"80","author":"Kouidhi","year":"2015","journal-title":"Microb. Pathog."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/978-3-319-11038-7_2","article-title":"Biofilm-based implant infections in orthopaedics","volume":"830","author":"Arciola","year":"2015","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1177\/039139880502801103","article-title":"Biofilm in implant infections: Its production and regulation","volume":"28","author":"Costerton","year":"2005","journal-title":"Int. J. Artif. Organ."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.micpath.2017.12.065","article-title":"Protective effects of thymol on LPS-induced acute lung injury in mice","volume":"116","author":"Yao","year":"2018","journal-title":"Microb. Pathog."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1053\/j.ajkd.2016.11.008","article-title":"Intraperitoneal vancomycin plus either oral moxifloxacin or intraperitoneal ceftazidime for the treatment of peritoneal dialysis\u2212related peritonitis: A randomized controlled pilot study","volume":"70","author":"Xu","year":"2017","journal-title":"Am. J. Kidney Dis."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Eto, D., Lao, C., DiToro, D., Barnett, B., Escobar, T.C., Kageyama, R., Yusuf, I., and Crotty, S. (2011). IL-21 and IL-6 are critical for different aspects of B cell immunity and redundantly induce optimal follicular helper CD4 T cell (Tfh) differentiation. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0017739"},{"key":"ref_49","first-page":"1","article-title":"Graft-derived IL-6 amplifies proliferation and survival of effector T cells that drive alloimmune-mediated vascular rejection","volume":"100","author":"Rey","year":"2016","journal-title":"Transplantation"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.ejphar.2018.06.003","article-title":"Thymol alleviates lipopolysaccharide-stimulated inflammatory response via downregulation of RhoA-mediated NF-\u03baB signalling pathway in human peritoneal mesothelial cells","volume":"833","author":"Wang","year":"2018","journal-title":"Eur. J. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1080\/13880209.2019.1674342","article-title":"The antibacterial mechanism of oridonin against methicillin-resistant Staphylococcus aureus (MRSA)","volume":"57","author":"Yuan","year":"2019","journal-title":"Pharm. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1021\/acs.jnatprod.9b00317","article-title":"Natural alkaloid berberine activity against Pseudomonas aeruginosa MexXY-mediated aminoglycoside resistance: In silico and in vitro studies","volume":"7","author":"Laudadio","year":"2019","journal-title":"J. Nat. Prod."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.2217\/fmb-2019-0146","article-title":"Terpinen-4-ol inhibits the growth of Sporothrix schenckii complex and exhibits synergism with antifungal agents","volume":"14","author":"Brilhante","year":"2019","journal-title":"Future Microbiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.ijmm.2015.05.001","article-title":"Synergy between baicalein and penicillins against penicillinase-producing Staphylococcus aureus","volume":"6","author":"Qian","year":"2015","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.3389\/fmicb.2017.01715","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_56","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.3389\/fmicb.2016.01320","article-title":"Pseudomonas fluorescens filamentous hemagglutinin, an iron-regulated protein, is an important virulence factor that modulates bacterial pathogenicity","volume":"7","author":"Sun","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5804","DOI":"10.1128\/AAC.01296-12","article-title":"Activity of gallidermin on Staphylococcus aureus and Staphylococcus epidermidis biofilms","volume":"56","author":"Saising","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.jep.2011.06.039","article-title":"Synergistic effects of baicalein with ciprofloxacin against NorA over-expressed methicillin-resistant Staphylococcus aureus (MRSA) and inhibition of MRSA pyruvate kinase","volume":"137","author":"Chan","year":"2011","journal-title":"J. Ethnopharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1136\/jcp.42.8.872","article-title":"New method for detecting slime production by coagulase negative staphylococci","volume":"42","author":"Freeman","year":"1989","journal-title":"J. Clin. Pathol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1007\/s00005-010-0079-9","article-title":"Slime production by Staphylococcus aureus and Staphylococcus epidermidis strains isolated from patients with diabetic foot ulcers","volume":"58","author":"Podbielska","year":"2010","journal-title":"Arch. Immunol. Exp."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"8113","DOI":"10.1073\/pnas.0610226104","article-title":"The cidA murein hydrolase regulator contributes to DNA release and biofilm development in Staphylococcus aureus","volume":"104","author":"Rice","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Ouyang, P., He, X., Yuan, Z.W., Yin, Z.Q., Fu, H., Lin, J., He, C., Liang, X., Lv, C., and Shu, G. (2018). Erianin against Staphylococcus aureus Infection via Inhibiting Sortase A. Toxins, 10.","DOI":"10.3390\/toxins10100385"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/nprot.2008.73","article-title":"Analyzing real-time PCR data by the comparative C(T) method","volume":"3","author":"Thomas","year":"2008","journal-title":"Nat. Protoc."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1093\/jac\/dks002","article-title":"Synergistic antibacterial efficacy of early combination treatment with tobramycin and quorum-sensing inhibitors against Pseudomonas aeruginosa in an intraperitoneal foreign-body infection mouse model","volume":"67","author":"Christensen","year":"2012","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Luo, J., Dong, B., Wang, K., Cai, S., Liu, T., Cheng, X., Lei, D., Chen, Y., Li, Y., and Kong, J. (2017). Baicalin inhibits biofilm formation, attenuates the quorum sensing-controlled virulence and enhances Pseudomonas aeruginosa clearance in a mouse peritoneal implant infection model. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0176883"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1007\/s00264-017-3477-3","article-title":"Inhibition of biofilm formation on iodine-supported titanium implants","volume":"41","author":"Inoue","year":"2017","journal-title":"Methods Int. Orthop."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/978-1-4939-1050-2_3","article-title":"Tissue processing and hematoxylin and eosin staining","volume":"1180","author":"Feldman","year":"2014","journal-title":"Methods Mol. Biol."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/8\/1\/99\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:19:27Z","timestamp":1760361567000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/8\/1\/99"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,10]]},"references-count":67,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,1]]}},"alternative-id":["microorganisms8010099"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms8010099","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,10]]}}}