{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T05:19:02Z","timestamp":1783055942261,"version":"3.54.6"},"reference-count":74,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The rise in antimicrobial resistance and the resilience of microbial biofilms demand innovative strategies that combine, for instance, membrane-active agents with marketed drugs. Arginine-based surfactants are promising alternatives to conventional quaternary ammonium compounds, but comparative data on their antimicrobial, antibiofilm and modulatory activities remain limited. Five arginine-derived surfactants, the single-chain N\u03b1-lauroyl-L-arginine methyl ester (LAM) and ethyl ester (LAE), together with their double-chain homologues LANHC3, LANHC5 and LANHC8 were evaluated against Gram-positive and Gram-negative bacteria and four Candida spp. Minimum inhibitory (MIC) and lethal (MLC) concentrations were determined by broth microdilution method. Antibiofilm activity was assessed through minimum biofilm inhibitory (MBIC) and eradication (MBEC) concentrations. Checkerboard assays were used to evaluate the synergism between the surfactants and conventional therapeutic antibacterial and antifungal agents. LANHC3 and LANHC8 exhibited uniform antibacterial MICs of 19.53 \u00b5g\/mL, while LAM and LANHC5 showed MICs of 19.53 \u00b5g\/mL for most strains, with Enterococcus faecalis requiring 39.06 \u00b5g\/mL. LANHC3 was the most potent surfactant over Candida spp. With MICs of 9.76 \u00b5g\/mL for all species, and similarly to LAM, both were fungicidal at 39.06 \u00b5g\/mL. LAM and LANHC3 also showed the lowest MBIC and MBEC values, inhibiting the Candida biofilm formation at 39.06 \u00b5g\/mL and eradicating mature biofilms at 78.12 \u00b5g\/mL, while the other surfactants required higher concentrations to disrupt the microbial biofilms. Synergic or additive interactions were found between the surfactants and selected \u03b2-lactam and macrolide antibiotics, as well as azole antifungals, with no antagonism observed. LAM and particularly LANHC3 combined broad-spectrum antimicrobial activity, relevant antibiofilm effects and the ability to potentiate the activity of conventional agents, supporting their choice as alternative or complementary antimicrobial adjuvants over resistant microorganisms and their biofilms.<\/jats:p>","DOI":"10.3390\/ijms27135936","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T12:41:38Z","timestamp":1782909698000},"page":"5936","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Single- and Double-Chain Arginine-Derived Surfactants: Antimicrobial, Antibiofilm and Synergistic Activities"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6380-1786","authenticated-orcid":false,"given":"Rafaela Gomes","family":"Bezerra","sequence":"first","affiliation":[{"name":"Graduate Program in Pharmaceutical Innovation, Federal University of Amap\u00e1 (UNIFAP), Macap\u00e1 68903-419, Brazil"},{"name":"Department of Pharmacy (DFAR), Faculty of Pharmacy, Dentistry and Nursing (FFOE), Federal University of Cear\u00e1 (UFC), Fortaleza 60430-372, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3696-021X","authenticated-orcid":false,"given":"Lourdes","family":"P\u00e9rez","sequence":"additional","affiliation":[{"name":"Department of Surfactants and Nanobiotechnology, Instituto de Qu\u00edmica Avanzada de Catalu\u00f1a, Centro Superior de Investigaciones Cient\u00edficas IQAC-CSIC, 08034 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8554-5189","authenticated-orcid":false,"given":"Zakaria","family":"Hafidi","sequence":"additional","affiliation":[{"name":"Department of Surfactants and Nanobiotechnology, Instituto de Qu\u00edmica Avanzada de Catalu\u00f1a, Centro Superior de Investigaciones Cient\u00edficas IQAC-CSIC, 08034 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7366-1622","authenticated-orcid":false,"given":"Francisco F\u00e1bio Oliveira","family":"de Sousa","sequence":"additional","affiliation":[{"name":"Graduate Program in Pharmaceutical Innovation, Federal University of Amap\u00e1 (UNIFAP), Macap\u00e1 68903-419, Brazil"},{"name":"Laboratory of Quality Control, Bromatology & Microbiology, School of Pharmacy, Department of Biological & Health Sciences, Federal University of Amap\u00e1 (UNIFAP), Macap\u00e1 68903-419, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100947","DOI":"10.1016\/j.lanmic.2024.07.010","article-title":"Antimicrobial Resistance: A Concise Update","volume":"6","author":"Ho","year":"2025","journal-title":"Lancet Microbe"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1080\/1040841X.2024.2313024","article-title":"Antibiotic Resistance: A Global Crisis, Problems and Solutions","volume":"50","author":"Aggarwal","year":"2024","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1016\/S0140-6736(24)01867-1","article-title":"Global Burden of Bacterial Antimicrobial Resistance 1990\u20132021: A Systematic Analysis with Forecasts to 2050","volume":"404","author":"Naghavi","year":"2024","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/S0140-6736(21)02724-0","article-title":"Global Burden of Bacterial Antimicrobial Resistance in 2019: A Systematic Analysis","volume":"399","author":"Murray","year":"2022","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"881","DOI":"10.3201\/eid0809.020063","article-title":"Biofilms: Microbial Life on Surfaces","volume":"8","author":"Donlan","year":"2002","journal-title":"Emerg. Infect. Dis."},{"key":"ref_6","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_7","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1007\/s10096-015-2323-z","article-title":"Biofilm-Specific Antibiotic Tolerance and Resistance","volume":"34","author":"Olsen","year":"2015","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1093\/femsre\/fux010","article-title":"Molecular Mechanisms of Biofilm-Based Antibiotic Resistance and Tolerance in Pathogenic Bacteria","volume":"41","author":"Hall","year":"2017","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1007\/s44371-025-00152-9","article-title":"Principles of Green Chemistry: Building a Sustainable Future","volume":"2","author":"Kurul","year":"2025","journal-title":"Discov. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"101884","DOI":"10.1016\/j.cocis.2024.101884","article-title":"Development of Amino Acid-Based Surfactants: From Synthesis to Applications","volume":"75","author":"Holmberg","year":"2025","journal-title":"Curr. Opin. Colloid Interface Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.cis.2015.11.007","article-title":"Amino Acid\u2013Based Surfactants: New Antimicrobial Agents","volume":"228","author":"Pinazo","year":"2016","journal-title":"Adv. Colloid Interface Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.ejbt.2021.02.002","article-title":"Production of Green Surfactants: Market Prospects","volume":"51","author":"Farias","year":"2021","journal-title":"Electron. J. Biotechnol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"139611","DOI":"10.1016\/j.jhazmat.2025.139611","article-title":"Ecological Assessment and Corrosion Inhibition Potential of Novel Double-Chain Arginine-Based Cationic Surfactants","volume":"497","author":"Bautista","year":"2025","journal-title":"J. Hazard. Mater."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"116819","DOI":"10.1016\/j.molliq.2021.116819","article-title":"Green Cationic Arginine Surfactants: Influence of the Polar Head Cationic Character on the Self-Aggregation and Biological Properties","volume":"339","author":"Pons","year":"2021","journal-title":"J. Mol. Liq."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1007\/s00726-014-1744-9","article-title":"Biological and Surface-Active Properties of Double-Chain Cationic Amino Acid-Based Surfactants","volume":"46","author":"Greber","year":"2014","journal-title":"Amino Acids"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"114762","DOI":"10.1016\/j.colsurfb.2025.114762","article-title":"Antimicrobial and Biofilm-Eradicating Properties of Simple Double-Chain Arginine-Based Surfactants","volume":"253","author":"Hafidi","year":"2025","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.cocis.2019.11.009","article-title":"Structure\u2013Activity Relationship of Cationic Surfactants as Antimicrobial Agents","volume":"45","author":"Zhou","year":"2020","journal-title":"Curr. Opin. Colloid Interface Sci."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Garc\u00eda, M.T., Mor\u00e1n, M.C., Pons, R., Hafidi, Z., Bautista, E., Vazquez, S., and P\u00e9rez, L. (2025). Arginine-Derived Cationic Surfactants Containing Phenylalanine and Tryptophan: Evaluation of Antifungal Activity, Biofilm Eradication, Cytotoxicity, and Ecotoxicity. J. Xenobiot., 15.","DOI":"10.3390\/jox15050140"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Perez, L., Hafidi, Z., Pinazo, A., Garc\u00eda, M.T., Mart\u00edn-Pastor, M., and Sousa, F.F.O.d. (2023). Zein Nanoparticles Containing Arginine-Phenylalanine-Based Surfactants: Stability, Antimicrobial and Hemolytic Activity. Nanomaterials, 13.","DOI":"10.3390\/nano13010200"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Sousa, F.F.O.d., Pinazo, A., Hafidi, Z., Garc\u00eda, M.T., Bautista, E., Moran, M.d.C., and P\u00e9rez, L. (2023). Arginine Gemini-Based Surfactants for Antimicrobial and Antibiofilm Applications: Molecular Interactions, Skin-Related Anti-Enzymatic Activity and Cytotoxicity. Molecules, 28.","DOI":"10.3390\/molecules28186570"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1039\/C2SM26670A","article-title":"Role of Aggregate Size in the Hemolytic and Antimicrobial Activity of Colloidal Solutions Based on Single and Gemini Surfactants from Arginine","volume":"9","author":"Tavano","year":"2013","journal-title":"Soft Matter"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.colsurfb.2016.01.020","article-title":"New Cationic Vesicles Prepared with Double Chain Surfactants from Arginine: Role of the Hydrophobic Group on the Antimicrobial Activity and Cytotoxicity","volume":"141","author":"Pinazo","year":"2016","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Pinazo, A., Pons, R., Marqu\u00e9s, A., Farfan, M., da Silva, A., and Perez, L. (2020). Biocompatible Catanionic Vesicles from Arginine-Based Surfactants: A New Strategy to Tune the Antimicrobial Activity and Cytotoxicity of Vesicular Systems. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12090857"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"307","DOI":"10.15698\/mic2019.07.683","article-title":"Adaptive Bacterial Response to Low Level Chlorhexidine Exposure and Its Implications for Hand Hygiene","volume":"6","author":"Kampf","year":"2019","journal-title":"Microb. Cell"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Pereira, A.P., Antunes, P., Peixe, L., Freitas, A.R., and Novais, C. (2024). Current Insights into the Effects of Cationic Biocides Exposure on Enterococcus spp.. Front. Microbiol., 15.","DOI":"10.3389\/fmicb.2024.1392018"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"421","DOI":"10.4161\/viru.21282","article-title":"Intrinsic and Acquired Resistance Mechanisms in Enterococcus","volume":"3","author":"Hollenbeck","year":"2012","journal-title":"Virulence"},{"key":"ref_27","unstructured":"Rapp, R.P., and Record, K.E. (2006). Gram-Negative Bacteria. Management of Antimicrobials in Infectious Diseases, Humana Press."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Killough, M., Rodgers, A.M., and Ingram, R.J. (2022). Pseudomonas Aeruginosa: Recent Advances in Vaccine Development. Vaccines, 10.","DOI":"10.3390\/vaccines10071100"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e01825-24","DOI":"10.1128\/aac.01825-24","article-title":"Regulation, Structure, and Activity of the Pseudomonas Aeruginosa MexXY Efflux System","volume":"69","author":"Kavanaugh","year":"2025","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1007\/s11274-025-04302-0","article-title":"Advancements in Escherichia Coli Secretion Systems for Enhanced Recombinant Protein Production","volume":"41","author":"Lokireddy","year":"2025","journal-title":"World J. Microbiol. Biotechnol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"101117","DOI":"10.1016\/j.jpha.2024.101117","article-title":"Advances and Mechanisms of Traditional Chinese Medicine and Its Active Ingredients against Antibiotic-Resistant Escherichia Coli Infections","volume":"15","author":"Yang","year":"2025","journal-title":"J. Pharm. Anal."},{"key":"ref_32","unstructured":"Wilson, M.G., and Pandey, S. (2026). Pseudomonas Aeruginosa. StatPearls, StatPearls Publishing."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"115436","DOI":"10.1016\/j.ejmech.2023.115436","article-title":"New Miconazole-Based Azoles Derived from Eugenol Show Activity against Candida Spp. and Cryptococcus gattii by Inhibiting the Fungal Ergosterol Biosynthesis","volume":"256","author":"Reis","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"179139","DOI":"10.1016\/j.scitotenv.2025.179139","article-title":"Antifungal Resistance in Yeasts from One Health Perspective: A Brazilian Study","volume":"973","author":"Bastos","year":"2025","journal-title":"Sci. Total Environ."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1093\/mmy\/myaa031","article-title":"Update on Candida Krusei, a Potential Multidrug-Resistant Pathogen","volume":"59","author":"Jamiu","year":"2021","journal-title":"Med. Mycol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Rigopoulos, D. (2023). Candidiasis. European Handbook of Dermatological Treatments, Springer.","DOI":"10.1007\/978-3-031-15130-9_12"},{"key":"ref_37","first-page":"355","article-title":"Candida Krusei Pericarditis: A Case Report and Review of the Literature","volume":"47","author":"Qaedi","year":"2024","journal-title":"New Microbiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"109164","DOI":"10.1016\/j.foodcont.2022.109164","article-title":"Developing Ethyl Lauroyl Arginate Antimicrobial Films to Combat Listeria Monocytogenes in Cured Ham","volume":"141","author":"Mitchell","year":"2022","journal-title":"Food Control"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1017\/S0033583508004721","article-title":"Interactions of Surfactants with Lipid Membranes","volume":"41","author":"Heerklotz","year":"2008","journal-title":"Q. Rev. Biophys."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1007\/s10529-020-03054-1","article-title":"Surfactants: Physicochemical Interactions with Biological Macromolecules","volume":"43","author":"Banat","year":"2021","journal-title":"Biotechnol. Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.1007\/s12010-015-1712-1","article-title":"Surfactant\u2013Amino Acid and Surfactant\u2013Surfactant Interactions in Aqueous Medium: A Review","volume":"176","author":"Malik","year":"2015","journal-title":"Appl. Biochem. Biotechnol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"114823","DOI":"10.1016\/j.molliq.2020.114823","article-title":"Effects of Fatty Acyl Chains on the Interfacial Rheological Behaviors of Amino Acid Surfactants","volume":"325","author":"Wang","year":"2021","journal-title":"J. Mol. Liq."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1007\/BF01520720","article-title":"Action of Surface-Active Substances on Biological Membranes V. Hemolytic, Lytic and Membrane-Perturbing Effects of N-Lauroyl Derivatives of Amino Acids with Aliphatic Side Chains","volume":"257","author":"Zaslavsky","year":"1979","journal-title":"Colloid Polym. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.ijfoodmicro.2013.06.017","article-title":"Antimicrobial Properties of Lauric Arginate Alone or in Combination with Essential Oils in Tryptic Soy Broth and 2% Reduced Fat Milk","volume":"166","author":"Ma","year":"2013","journal-title":"Int. J. Food Microbiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4207","DOI":"10.3168\/jds.2009-2150","article-title":"N\u03b1-Lauroyl-L-Arginine Ethylester Monohydrochloride Reduces Bacterial Growth in Pasteurized Milk","volume":"92","author":"Woodcock","year":"2009","journal-title":"J. Dairy Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1590\/S1413-86702008000600016","article-title":"Biofilms: Microbes and Disease","volume":"12","author":"Aparna","year":"2008","journal-title":"Braz. J. Infect. Dis."},{"key":"ref_47","first-page":"107","article-title":"Antimicrobial Activity in Bacterial Biofilms","volume":"26","author":"Pascual","year":"2008","journal-title":"Enferm. Infecc. Microbiol. Clin."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1007\/s00726-023-03296-z","article-title":"Biocidal and Antibiofilm Activities of Arginine-Based Surfactants against Candida Isolates","volume":"55","author":"Fait","year":"2023","journal-title":"Amino Acids"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"112017","DOI":"10.1016\/j.colsurfb.2021.112017","article-title":"Arginine-Phenylalanine and Arginine-Tryptophan-Based Surfactants as New Biocompatible Antifungal Agents and Their Synergistic Effect with Amphotericin B against Fluconazole-Resistant Candida Strains","volume":"207","author":"Cavalcanti","year":"2021","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1146\/annurev.mi.49.100195.003431","article-title":"Microbial Biofilms","volume":"49","author":"Costerton","year":"1995","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"102581","DOI":"10.1016\/j.cis.2021.102581","article-title":"Cationic Gemini Surfactant Properties, Its Potential as a Promising Bioapplication Candidate, and Strategies for Improving Its Biocompatibility: A Review","volume":"299","author":"Ahmady","year":"2022","journal-title":"Adv. Colloid Interface Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"114424","DOI":"10.1016\/j.molliq.2020.114424","article-title":"Formation and Potential Application of Micelles Composed of Biocompatible N-Lauroyl-Amino Acid Ionic Liquids Surfactant","volume":"320","author":"Moshikur","year":"2020","journal-title":"J. Mol. Liq."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1002\/jsde.12402","article-title":"Modulation in Aggregation Behavior of Cationic Surfactant in Presence of Fluoroquinolone Drug: A Physicochemical Approach","volume":"23","author":"Pathania","year":"2020","journal-title":"J. Surfactants Deterg."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"106448","DOI":"10.1016\/j.bioorg.2023.106448","article-title":"A Win-Win Scenario for Antibacterial Activity and Skin Mildness of Cationic Surfactants Based on the Modulation of Host-Guest Supramolecular Conformation","volume":"134","author":"Wang","year":"2023","journal-title":"Bioorg. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1097\/MRM.0b013e3283587727","article-title":"\u03b2-Lactams: Chemical Structure, Mode of Action and Mechanisms of Resistance","volume":"24","author":"Fernandes","year":"2013","journal-title":"Rev. Res. Med. Microbiol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Yuli, I., Tzafrir, I., and Salama, P. (2023). Compatibility Investigation of Cationic Surfactants with Anionic Species. Cosmetics, 10.","DOI":"10.3390\/cosmetics10020045"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"348","DOI":"10.2146\/ajhp080059","article-title":"Drug Incompatibility Chemistry","volume":"66","author":"Newton","year":"2009","journal-title":"Am. J. Health-Syst. Pharm."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Turner, J., Muraoka, A., Bedenbaugh, M., Childress, B., Pernot, L., Wiencek, M., and Peterson, Y.K. (2022). The Chemical Relationship Among Beta-Lactam Antibiotics and Potential Impacts on Reactivity and Decomposition. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.807955"},{"key":"ref_59","unstructured":"Thai, T., Salisbury, B.H., and Zito, P.M. (2023). Ciprofloxacin. StatPearls, StatPearls Publishing."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.ejmech.2018.01.078","article-title":"Ciprofloxacin Derivatives and Their Antibacterial Activities","volume":"146","author":"Zhang","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2752","DOI":"10.1128\/AAC.39.12.2752","article-title":"Antibacterial Action of Ciprofloxacin","volume":"39","author":"Mason","year":"1995","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.identj.2022.01.005","article-title":"Chlorhexidine in Dentistry: Pharmacology, Uses, and Adverse Effects","volume":"72","author":"Ouanounou","year":"2022","journal-title":"Int. Dent. J."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"101829","DOI":"10.1016\/j.cocis.2024.101829","article-title":"Combinatorial Therapies of Surfactant-like Antimicrobial Peptides and Antibiotics for Improved Therapeutic Efficacy","volume":"73","author":"Liao","year":"2024","journal-title":"Curr. Opin. Colloid Interface Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"9849","DOI":"10.1021\/ja8017863","article-title":"Biomolecular Engineering by Combinatorial Design and High-Throughput Screening: Small, Soluble Peptides That Permeabilize Membranes","volume":"130","author":"Rathinakumar","year":"2008","journal-title":"J. Am. Chem. Soc."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.phymed.2008.06.008","article-title":"Synergism between Natural Products and Antibiotics against Infectious Diseases","volume":"15","author":"Hemaiswarya","year":"2008","journal-title":"Phytomedicine"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Pinazo, A., P\u00e9rez, L., Del Carmen Mor\u00e1n, M., and Pons, R. (2019). Arginine-Based Surfactants: Synthesis, Aggregation Properties, and Applications. Biobased Surfactants: Synthesis, Properties, and Applications, AOCS Press.","DOI":"10.1016\/B978-0-12-812705-6.00013-7"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"139499","DOI":"10.1016\/j.cplett.2022.139499","article-title":"Review: Progress in Synthesis, Properties and Application of Amino Acid Surfactants","volume":"794","author":"Guo","year":"2022","journal-title":"Chem. Phys. Lett."},{"key":"ref_68","unstructured":"CLSI (2017). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts, Clinical and Laboratory Standards Institute. [4th ed.]. CLSI Standard M27."},{"key":"ref_69","unstructured":"CLSI (2024). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically, Clinical and Laboratory Standards Institute. [12th ed.]. CLSI Standard M07."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"107596","DOI":"10.1016\/j.micpath.2025.107596","article-title":"Exploring the Antifungal Potential and Action Mechanism of Pomegranate Peel Extract against Candida Species in Planktonic and Biofilm Conditions","volume":"204","author":"Ferreira","year":"2025","journal-title":"Microb. Pathog."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1111\/jam.13547","article-title":"Violacein Antimicrobial Activity on Staphylococcus Epidermidis and Synergistic Effect on Commercially Available Antibiotics","volume":"123","author":"Dodou","year":"2017","journal-title":"J. Appl. Microbiol."},{"key":"ref_72","first-page":"e58636","article-title":"Antimicrobial Synergy Testing by Inkjet Printer-Assisted Automated Checkerboard Array and Manual Time-Kill Methods","volume":"2019","author":"Kirby","year":"2019","journal-title":"J. Vis. Exp."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1093\/jac\/11.5.427","article-title":"The Fractional Inhibitory Concentration (FIC) Index as a Measure of Synergy","volume":"11","author":"Hall","year":"1983","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/jac\/dkg301","article-title":"Synergy, Antagonism, and What the Chequerboard Puts between Them","volume":"52","author":"Odds","year":"2003","journal-title":"J. Antimicrob. Chemother."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/5936\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T04:45:55Z","timestamp":1783053955000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/5936"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,1]]},"references-count":74,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27135936"],"URL":"https:\/\/doi.org\/10.3390\/ijms27135936","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,1]]}}}