{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T14:00:42Z","timestamp":1794060042449,"version":"4.8.0"},"reference-count":76,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation (NRF) of Korea","doi-asserted-by":"crossref","award":["RS-2023-00241461"],"award-info":[{"award-number":["RS-2023-00241461"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background\/Objectives:\u00a0Staphylococcus aureus is a well-known opportunistic pathogen that causes a wide range of infections, from cutaneous blemishes to potentially fatal systemic diseases. The increasing prevalence of antibiotic-resistant bacteria highlights the critical need for alternative therapeutic methods that target virulence factors rather than growth. Methods: The antibacterial activity of 3-fluorocatechol (3-FC) against bacterial and fungal pathogens (e.g., Candida albicans) was determined by broth microdilution to establish the lowest inhibitory concentration. The antibiofilm impact of 3-FC against S. aureus was evaluated using crystal violet staining and viable colony counts, followed by scanning electron microscopy to visualize the biofilm architecture. The methanol extraction method was used to quantify staphyloxanthin synthesis in S. aureus cells. Furthermore, in silico molecular docking was used to evaluate 3-FC binding interactions and provide mechanistic insight into its impacts on S. aureus biofilms and virulence-associated factors. Results: Although the study showed that 3-FC exhibits weak antibacterial activity against S. aureus (MIC &gt; 2048 \u00b5g\/mL), it shows effective inhibition of up to 86.5% at sub-inhibitory doses during the initial stage of biofilm formation. The CFU enumeration also confirms the significant reduction of viable cell count of S. aureus in the presence of sub-MIC of 3-FC. The SEM analysis confirms disruption of the S. aureus biofilm architecture in the presence of a sub-MIC of 3-FC. Furthermore, the eradication of mature S. aureus biofilm at a sub-MIC dose of 3-FC was 60.6%. 3-FC significantly reduced staphyloxanthin formation, a vital antioxidant pigment that contributes to bacterial pathogenicity, with a maximal suppression of 66.3% at 2048 \u00b5g\/mL. Molecular docking analyses provide further insight into the molecular basis of 3-FC activity, revealing strong binding affinities with numerous S. aureus virulence regulators and enzymes, suggesting interference with quorum-sensing, adhesion, and oxidative-stress response pathways. Conclusions: Collectively, our findings indicate that 3-FC has antibiofilm and antivirulence properties against S. aureus. Furthermore, this study suggests 3-FC as a viable structural scaffold for the development of a novel anti-infective agent to treat chronic staphylococcal infections.<\/jats:p>","DOI":"10.3390\/antibiotics14121240","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T14:52:24Z","timestamp":1765205544000},"page":"1240","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Attenuation of Staphylococcus aureus Biofilms and Virulence by 3-Fluorocatechol"],"prefix":"10.3390","volume":"14","author":[{"given":"Taehyeong","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Applied Biosciences, Kyungpook National University, Daegu 41566, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9314-9124","authenticated-orcid":false,"given":"Nazia","family":"Tabassum","sequence":"additional","affiliation":[{"name":"Marine Integrated Biomedical Technology Center, The National Key Research Institutes in Universities, Pukyong National University, Busan 48513, Republic of Korea"},{"name":"Research Center for Marine Integrated Bionics Technology, Pukyong National University, Busan 48513, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aqib","family":"Javaid","sequence":"additional","affiliation":[{"name":"Interdisciplinary Program of Marine and Fisheries Sciences and Convergent Technology, Pukyong National University, Busan 48513, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4902-3188","authenticated-orcid":false,"given":"Fazlurrahman","family":"Khan","sequence":"additional","affiliation":[{"name":"Marine Integrated Biomedical Technology Center, The National Key Research Institutes in Universities, Pukyong National University, Busan 48513, Republic of Korea"},{"name":"Research Center for Marine Integrated Bionics Technology, Pukyong National University, Busan 48513, Republic of Korea"},{"name":"Interdisciplinary Program of Marine and Fisheries Sciences and Convergent Technology, Pukyong National University, Busan 48513, Republic of Korea"},{"name":"Ocean and Fisheries Development International Cooperation Institute, Pukyong National University, Busan 48513, Republic of Korea"},{"name":"International Graduate Program of Fisheries Science, Pukyong National University, Busan 48513, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Touaitia, R., Mairi, A., Ibrahim, N.A., Basher, N.S., Idres, T., and Touati, A. (2025). Staphylococcus aureus: A Review of the Pathogenesis and Virulence Mechanisms. Antibiotics, 14.","DOI":"10.3390\/antibiotics14050470"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2464","DOI":"10.1172\/JCI38226","article-title":"Reemergence of antibiotic-resistant Staphylococcus aureus in the genomics era","volume":"119","author":"DeLeo","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Gajd\u00e1cs, M. (2019). The Continuing Threat of Methicillin-Resistant Staphylococcus aureus. Antibiotics, 8.","DOI":"10.3390\/antibiotics8020052"},{"key":"ref_4","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. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Pietrocola, G., Campoccia, D., Motta, C., Montanaro, L., Arciola, C.R., and Speziale, P. (2022). Colonization and Infection of Indwelling Medical Devices by Staphylococcus aureus with an Emphasis on Orthopedic Implants. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23115958"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1039\/C9MD00044E","article-title":"Methicillin-resistant Staphylococcus aureus (MRSA): Antibiotic-resistance and the biofilm phenotype","volume":"10","author":"Craft","year":"2019","journal-title":"MedChemComm"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1097\/MRM.0000000000000223","article-title":"Staphylococcus aureus biofilms: An opportunistic pathogen with multidrug resistance","volume":"32","author":"Oliveira","year":"2021","journal-title":"Rev. Res. Med. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Idrees, M., Sawant, S., Karodia, N., and Rahman, A. (2021). Staphylococcus aureus Biofilm: Morphology, Genetics, Pathogenesis and Treatment Strategies. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph18147602"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Sedarat, Z., and Taylor-Robinson, A.W. (2022). Biofilm Formation by Pathogenic Bacteria: Applying a Staphylococcus aureus Model to Appraise Potential Targets for Therapeutic Intervention. Pathogens, 11.","DOI":"10.3390\/pathogens11040388"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1002\/phar.2806","article-title":"Current therapies and challenges for the treatment of Staphylococcus aureus biofilm-related infections","volume":"43","author":"Tran","year":"2023","journal-title":"Pharmacother. J. Hum. Pharmacol. Drug Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.csbj.2025.01.021","article-title":"Structural characteristics, functions, and counteracting strategies of biofilms in Staphylococcus aureus","volume":"27","author":"Xia","year":"2025","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Touati, A., Ibrahim, N.A., and Idres, T. (2025). Disarming Staphylococcus aureus: Review of Strategies Combating This Resilient Pathogen by Targeting Its Virulence. Pathogens, 14.","DOI":"10.3390\/pathogens14040386"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Wu, X., Wang, H., Xiong, J., Yang, G.-X., Hu, J.-F., Zhu, Q., and Chen, Z. (2024). Staphylococcus aureus biofilm: Formulation, regulatory, and emerging natural products-derived therapeutics. Biofilm, 7.","DOI":"10.1016\/j.bioflm.2023.100175"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"126340","DOI":"10.1016\/j.cej.2020.126340","article-title":"Antimicrobial property of halogenated catechols","volume":"403","author":"Liu","year":"2021","journal-title":"Chem. Eng. J."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Yam, K.C., D\u2019Angelo, I., Kalscheuer, R., Zhu, H., Wang, J.-X., Snieckus, V., Ly, L.H., Converse, P.J., Jacobs, W.R., and Strynadka, N. (2009). Studies of a Ring-Cleaving Dioxygenase Illuminate the Role of Cholesterol Metabolism in the Pathogenesis of Mycobacterium tuberculosis. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000344"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3388","DOI":"10.1039\/b910500j","article-title":"The influence of catechol structure on the suicide-inactivation of tyrosinase","volume":"7","author":"Ramsden","year":"2009","journal-title":"Org. Biomol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.jsb.2012.11.007","article-title":"X-ray structures of 4-chlorocatechol 1,2-dioxygenase adducts with substituted catechols: New perspectives in the molecular basis of intradiol ring cleaving dioxygenases specificity","volume":"181","author":"Ferraroni","year":"2013","journal-title":"J. Struct. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.bioorg.2015.05.002","article-title":"Chemical intervention in bacterial lignin degradation pathways: Development of selective inhibitors for intradiol and extradiol catechol dioxygenases","volume":"60","author":"Sainsbury","year":"2015","journal-title":"Bioorg. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6315","DOI":"10.1021\/acs.jmedchem.9b01877","article-title":"Metabolic and Pharmaceutical Aspects of Fluorinated Compounds","volume":"63","author":"Johnson","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Campana, R., Mangiaterra, G., Tiboni, M., Frangipani, E., Biavasco, F., Lucarini, S., and Citterio, B. (2020). A Fluorinated Analogue of Marine Bisindole Alkaloid 2,2-Bis(6-bromo-1H-indol-3-yl)ethanamine as Potential Anti-Biofilm Agent and Antibiotic Adjuvant Against Staphylococcus aureus. Pharmaceuticals, 13.","DOI":"10.3390\/ph13090210"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.ejmech.2016.08.017","article-title":"Novel fluorinated pyrrolomycins as potent anti-staphylococcal biofilm agents: Design, synthesis, pharmacokinetics and antibacterial activities","volume":"124","author":"Yang","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Elmogy, S., Ismail, M.A., Hassan, R.Y.A., Noureldeen, A., Darwish, H., Fayad, E., Elsaid, F., and Elsayed, A. (2021). Biological Insights of Fluoroaryl-2,2\u2032-Bichalcophene Compounds on Multi-Drug Resistant Staphylococcus aureus. Molecules, 26.","DOI":"10.3390\/molecules26010139"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.jconrel.2024.03.021","article-title":"Lipase and pH-responsive diblock copolymers featuring fluorocarbon and carboxyl betaine for methicillin-resistant Staphylococcus aureus infections","volume":"369","author":"Xiao","year":"2024","journal-title":"J. Control. Release"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1128\/aem.47.3.500-505.1984","article-title":"Suicide Inactivation of Catechol 2,3-Dioxygenase from Pseudomonas putida mt-2 by 3-Halocatechols","volume":"47","author":"Bartels","year":"1984","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.1128\/AEM.70.3.1804-1810.2004","article-title":"Construction of chimeric catechol 2,3-dioxygenase exhibiting improved activity against the suicide inhibitor 4-methylcatechol","volume":"70","author":"Okuta","year":"2004","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Ma, Y., Xu, Y., Yestrepsky, B.D., Sorenson, R.J., Chen, M., Larsen, S.D., and Sun, H. (2012). Novel Inhibitors of Staphylococcus aureus Virulence Gene Expression and Biofilm Formation. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0047255"},{"key":"ref_27","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_28","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1002\/cmdc.202000677","article-title":"Therapeutic Strategies To Counteract Antibiotic Resistance in MRSA Biofilm-Associated Infections","volume":"16","author":"Cascioferro","year":"2021","journal-title":"ChemMedChem"},{"key":"ref_29","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_30","doi-asserted-by":"crossref","unstructured":"Chan, L.C., Lee, H.K., Wang, L., Chaili, S., Xiong, Y.Q., Bayer, A.S., Proctor, R.A., and Yeaman, M.R. (2023). Diflunisal and Analogue Pharmacophores Mediating Suppression of Virulence Phenotypes in Staphylococcus aureus. Antibiotics, 12.","DOI":"10.3390\/antibiotics12071180"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/j.jfluchem.2008.05.016","article-title":"Use of fluorinated functionality in enzyme inhibitor development: Mechanistic and analytical advantages","volume":"129","author":"Berkowitz","year":"2008","journal-title":"J. Fluor. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1002\/iub.348","article-title":"Suicide inactivation of the diphenolase and monophenolase activities of tyrosinase","volume":"62","author":"Varon","year":"2010","journal-title":"IUBMB Life"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1124\/dmd.116.071654","article-title":"Analysis of Mechanism-Based Inhibition of CYP 3A4 by a Series of Fluoroquinolone Antibacterial Agents","volume":"44","author":"Watanabe","year":"2016","journal-title":"Drug Metab. Dispos."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Razaviamri, S., Wang, K., Liu, B., and Lee, B.P. (2021). Catechol-Based Antimicrobial Polymers. Molecules, 26.","DOI":"10.3390\/molecules26030559"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Thebti, A., Meddeb, A., Ben Salem, I., Bakary, C., Ayari, S., Rezgui, F., Essafi-Benkhadir, K., Boudabous, A., and Ouzari, H.-I. (2023). Antimicrobial Activities and Mode of Flavonoid Actions. Antibiotics, 12.","DOI":"10.3390\/antibiotics12020225"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1021\/acsinfecdis.7b00134","article-title":"Halogenation of Biotin Protein Ligase Inhibitors Improves Whole Cell Activity against Staphylococcus aureus","volume":"4","author":"Paparella","year":"2018","journal-title":"ACS Infect. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.cbi.2016.09.010","article-title":"Contribution of reactive oxygen species to (+)-catechin-mediated bacterial lethality","volume":"258","author":"Ajiboye","year":"2016","journal-title":"Chem.-Biol. Interact."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"312","DOI":"10.3831\/KPI.2016.19.032","article-title":"Effect of Catechins, Green tea Extract and Methylxanthines in Combination with Gentamicin Against Staphylococcus aureus and Pseudomonas aeruginosa-Combination therapy against resistant bacteria","volume":"19","author":"Sarabandi","year":"2016","journal-title":"J. Pharmacopunct."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/S2221-1691(13)60133-1","article-title":"Antimicrobial activity of green tea extract against isolates of methicillin\u2013resistant Staphylococcus aureus and multi\u2013drug resistant Pseudomonas aeruginosa","volume":"3","author":"Radji","year":"2013","journal-title":"Asian Pac. J. Trop. Biomed."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"11567","DOI":"10.1039\/C5OB01859E","article-title":"Synthesis and antibiotic activity of oxazolidinone\u2013catechol conjugates against Pseudomonas aeruginosa","volume":"13","author":"Paulen","year":"2015","journal-title":"Org. Biomol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Ajiboye, T.O., Habibu, R.S., Saidu, K., Haliru, F.Z., Ajiboye, H.O., Aliyu, N.O., Ibitoye, O.B., Uwazie, J.N., Muritala, H.F., and Bello, S.A. (2017). Involvement of oxidative stress in protocatechuic acid-mediated bacterial lethality. MicrobiologyOpen, 6.","DOI":"10.1002\/mbo3.472"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Nov\u00e1s, M., and Matos, M.J. (2025). The Role of Trifluoromethyl and Trifluoromethoxy Groups in Medicinal Chemistry: Implications for Drug Design. Molecules, 30.","DOI":"10.3390\/molecules30143009"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1002\/cmdc.201900452","article-title":"Chalcogen OCF3 Isosteres Modulate Drug Properties without Introducing Inherent Liabilities","volume":"14","author":"Ghiazza","year":"2019","journal-title":"ChemMedChem"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Lagu, S.B., Yejella, R.P., Bhandare, R.R., and Shaik, A.B. (2020). Design, Synthesis, and Antibacterial and Antifungal Activities of Novel Trifluoromethyl and Trifluoromethoxy Substituted Chalcone Derivatives. Pharmaceuticals, 13.","DOI":"10.3390\/ph13110375"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"123","DOI":"10.4103\/phrev.phrev_43_16","article-title":"General Overview of Phenolics from Plant to Laboratory, Good Antibacterials or Not","volume":"11","author":"Aldulaimi","year":"2017","journal-title":"Pharmacogn. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Jothi, R., Sangavi, R., Kumar, P., Pandian, S.K., and Gowrishankar, S. (2021). Catechol thwarts virulent dimorphism in Candida albicans and potentiates the antifungal efficacy of azoles and polyenes. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-00485-2"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1021\/acsinfecdis.1c00402","article-title":"Modular Synthetic Routes to Fluorine-Containing Halogenated Phenazine and Acridine Agents That Induce Rapid Iron Starvation in Methicillin-Resistant Staphylococcus aureus Biofilms","volume":"8","author":"Liu","year":"2022","journal-title":"ACS Infect. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.micpath.2017.03.033","article-title":"Inhibitory effects of flavonoids on biofilm formation by Staphylococcus aureus that overexpresses efflux protein genes","volume":"107","author":"Lopes","year":"2017","journal-title":"Microb. Pathog."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Mandalari, G., Minuti, A., La Camera, E., Barreca, D., Romeo, O., and Nostro, A. (2023). Antimicrobial Susceptibility of Staphylococcus aureus Strains and Effect of Phloretin on Biofilm Formation. Curr. Microbiol., 80.","DOI":"10.1007\/s00284-023-03400-2"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Mastoor, S., Nazim, F., Rizwan-ul-Hasan, S., Ahmed, K., Khan, S., Ali, S.N., and Abidi, S.H. (2022). Analysis of the Antimicrobial and Anti-Biofilm Activity of Natural Compounds and Their Analogues against Staphylococcus aureus Isolates. Molecules, 27.","DOI":"10.3390\/molecules27206874"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1039\/C4RA08728C","article-title":"Bromophenazine derivatives with potent inhibition, dispersion and eradication activities against Staphylococcus aureus biofilms","volume":"5","author":"Garrison","year":"2015","journal-title":"RSC Adv."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1002\/jor.23291","article-title":"Vancomycin displays time-dependent eradication of mature Staphylococcus aureus biofilms","volume":"35","author":"Post","year":"2017","journal-title":"J. Orthop. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1097\/CORR.0000000000002251","article-title":"Halicin Is Effective Against Staphylococcus aureus Biofilms In Vitro","volume":"480","author":"Higashihira","year":"2022","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Yu, J., Rao, L., Zhan, L., Wang, B., Zhan, Q., Xu, Y., Zhao, H., Wang, X., Zhou, Y., and Guo, Y. (2021). The small molecule ZY-214-4 may reduce the virulence of Staphylococcus aureus by inhibiting pigment production. BMC Microbiol., 21.","DOI":"10.1186\/s12866-021-02113-5"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4950","DOI":"10.1128\/IAI.00204-06","article-title":"Staphyloxanthin Plays a Role in the Fitness of Staphylococcus aureus and Its Ability To Cope with Oxidative Stress","volume":"74","author":"Clauditz","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1126\/science.1153018","article-title":"A cholesterol biosynthesis inhibitor blocks Staphylococcus aureus virulence","volume":"319","author":"Liu","year":"2008","journal-title":"Science"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3869","DOI":"10.1021\/jm9001764","article-title":"Inhibition of Staphyloxanthin Virulence Factor Biosynthesis in Staphylococcus aureus: In Vitro, in Vivo, and Crystallographic Results","volume":"52","author":"Song","year":"2009","journal-title":"J. Med. Chem."},{"key":"ref_58","first-page":"277","article-title":"The antibiotic resistance crisis: Part 1: Causes and threats","volume":"40","author":"Ventola","year":"2015","journal-title":"Pharm. Ther."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/nprot.2007.521","article-title":"Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances","volume":"3","author":"Wiegand","year":"2008","journal-title":"Nat. Protoc."},{"key":"ref_60","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_61","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.mimet.2007.11.010","article-title":"Comparison of multiple methods for quantification of microbial biofilms grown in microtiter plates","volume":"72","author":"Peeters","year":"2008","journal-title":"J. Microbiol. Methods"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Khan, F., Oh, D., Chandika, P., Jo, D.-M., Bamunarachchi, N.I., Jung, W.-K., and Kim, Y.-M. (2022). Inhibitory activities of phloroglucinol-chitosan nanoparticles on mono- and dual-species biofilms of Candida albicans and bacteria. Colloids Surf. B Biointerfaces, 211.","DOI":"10.1016\/j.colsurfb.2021.112307"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3717","DOI":"10.1007\/s00253-021-11300-3","article-title":"Caffeine-loaded gold nanoparticles: Antibiofilm and anti-persister activities against pathogenic bacteria","volume":"105","author":"Khan","year":"2021","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"9873","DOI":"10.1021\/acsomega.2c06789","article-title":"Inhibition of Biofilm and Virulence Properties of Pathogenic Bacteria by Silver and Gold Nanoparticles Synthesized from Lactiplantibacillus sp. Strain C1","volume":"8","author":"Kang","year":"2023","journal-title":"ACS Omega"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1038\/nchembio.2003","article-title":"Small-molecule targeting of a diapophytoene desaturase inhibits S. aureus virulence","volume":"12","author":"Chen","year":"2016","journal-title":"Nat. Chem. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Johansson, M.U., Zoete, V., Michielin, O., and Guex, N. (2012). Defining and searching for structural motifs using DeepView\/Swiss-PdbViewer. BMC Bioinform., 13.","DOI":"10.1186\/1471-2105-13-173"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1002\/jcc.21256","article-title":"AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility","volume":"30","author":"Morris","year":"2009","journal-title":"J. Comput. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"6660","DOI":"10.1093\/emboj\/cdf619","article-title":"A novel variant of the immunoglobulin fold in surface adhesins of Staphylococcus aureus: Crystal structure of the fibrinogen-binding MSCRAMM, clumping factor A","volume":"21","author":"Deivanayagam","year":"2002","journal-title":"EMBO J."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"18586","DOI":"10.1074\/jbc.273.29.18586","article-title":"Characterization of the N-acetylglucosaminyltransferase activity involved in the biosynthesis of the Staphylococcus epidermidis polysaccharide intercellular adhesin","volume":"273","author":"Gerke","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3107","DOI":"10.1016\/j.jmb.2019.06.019","article-title":"Repurposing an Ancient Protein Core Structure: Structural Studies on FmtA, a Novel Esterase of Staphylococcus aureus","volume":"431","author":"Dalal","year":"2019","journal-title":"J. Mol. Biol."},{"key":"ref_71","first-page":"870","article-title":"Structural basis for the beta lactam resistance of PBP2a from methicillin-resistant Staphylococcus aureus","volume":"9","author":"Lim","year":"2002","journal-title":"Nat. Struct. Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"E2037","DOI":"10.1073\/pnas.1322125111","article-title":"Differential regulation of staphylococcal virulence by the sensor kinase SaeS in response to neutrophil-derived stimuli","volume":"111","author":"Flack","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Liu, Q., Yeo, W.S., and Bae, T. (2016). The SaeRS Two-Component System of Staphylococcus aureus. Genes, 7.","DOI":"10.3390\/genes7100081"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"24465","DOI":"10.1074\/jbc.M109.022624","article-title":"The structure of the Staphylococcus aureus sortase-substrate complex reveals how the universally conserved LPXTG sorting signal is recognized","volume":"284","author":"Suree","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/1758-2946-3-33","article-title":"Open Babel: An open chemical toolbox","volume":"3","author":"Banck","year":"2011","journal-title":"J. Cheminformatics"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3891","DOI":"10.1021\/acs.jcim.1c00203","article-title":"AutoDock Vina 1.2.0: New Docking Methods, Expanded Force Field, and Python Bindings","volume":"61","author":"Eberhardt","year":"2021","journal-title":"J. Chem. Inf. 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