Antimicrobial and antibiofilm activity of antidepressants Against Staphylococcus aureus
DOI:
https://doi.org/10.5433/1679-0367.2025v46n2p120Keywords:
Microbial Resistance, Drug Repurposing, Gram-Positive Bacteria, Cytotoxicity, Bacterial BiofilmsAbstract
Antimicrobial resistance represents a major health challenge, particularly due to the ability of Staphylococcus aureus to form biofilms and persist under antimicrobial pressure. In this context, drug repurposing has emerged as a promising strategy to identify alternative therapeutic options from approved drugs. This study aimed to evaluate the antimicrobial, antibiofilm, and cytotoxic activities of the antidepressants fluoxetine, paroxetine, and duloxetine against planktonic and biofilm-forming Staphylococcus aureus strains. Antibacterial activity was determined by broth microdilution assays to establish the minimum inhibitory concentration and minimum bactericidal concentration against Staphylococcus aureus ATCC 33591 and ATCC 29213. Antibiofilm activity was assessed in mature biofilms using cell viability assays and biomass quantification. Cytotoxicity was evaluated in RAW 264.7 macrophages using a cell viability assay, with calculation of mean effective concentration values. Fluoxetine and duloxetine exhibited lower inhibitory and bactericidal concentrations compared to paroxetine. In biofilm assays, fluoxetine and duloxetine significantly reduced biofilm cell viability and biomass, whereas paroxetine showed a less consistent effect. Cytotoxicity analysis revealed similar EC₅₀ values among the evaluated drugs, and the concentrations associated with relevant antibacterial and antibiofilm effects were approximately 20-fold higher than the EC₅₀ values determined in macrophages, indicating that, in this in vitro model, antimicrobial and antibiofilm activity occur in a concentration range accompanied by measurable cytotoxicity. Overall, the results indicate that antidepressants, particularly fluoxetine and duloxetine, exhibit in vitro antimicrobial and antibiofilm activity against Staphylococcus aureus, reinforcing the potential of these compounds for future drug repurposing studies.
Downloads
References
Ashburn TT, Thor KB. Drug repositioning: identifying and developing new uses for existing drugs. Nat Rev Drug Discov. 2004 Aug;3(8):673–683. doi:10.1038/nrd1468.
Avershina E, Shapovalova V, Shipulin G. Fighting antibiotic resistance in hospital-acquired infections: current state and emerging technologies in disease prevention, diagnostics and therapy. Front Microbiol. 2021;12:707918. doi:10.3389/fmicb.2021.707918.
Breckenridge A, Jacob R. Overcoming the legal and regulatory barriers to drug repurposing. Nat Rev Drug Discov. 2018 Aug;17(8):559–560. doi:10.1038/nrd.2018.92.
Cabral VPF, et al. Antibacterial activity of paroxetine against Staphylococcus aureus and possible mechanisms of action. Future Microbiol. 2023;18(7). doi:10.2217/fmb-2022-0232.
Cederlund H, Mårdh PA. Antibacterial activities of non-antibiotic drugs. J Antimicrob Chemother. 1993 Sep;32(3):355–365. doi:10.1093/jac/32.3.355.
Christaki E, Marcou M, Tofarides A. Antimicrobial resistance in bacteria: mechanisms, evolution, and persistence. J Mol Evol. 2020 Jan;88(1):26–40. doi:10.1007/s00239-019-09914-3.
Clinical and Laboratory Standards Institute (CLSI). Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. 9th ed. Wayne: CLSI; 2012. CLSI document M07-A9.
Foletto VS, et al. Repositioning of fluoxetine and paroxetine: study of potential antibacterial activity and its combination with ciprofloxacin. Med Chem Res. 2020;29(3):495–503. doi:10.1007/s00044-020-02507-6.
Frieri M, Kumar K, Boutin A. Antibiotic resistance. J Infect Public Health. 2017 Jul-Aug;10(4):369–378.
Harbarth S, et al. Antimicrobial resistance: one world, one fight! Antimicrob Resist Infect Control. 2015;4:49. doi:10.1186/s13756-015-0091-2.
Hengzhuang W, Høiby N, Ciofu O. Pharmacokinetics and pharmacodynamics of antibiotics in biofilm infections of Pseudomonas aeruginosa in vitro and in vivo. Methods Mol Biol. 2014;1147:239–254. doi:10.1007/978-1-4939-0467-9_17.
Kowalska M, et al. Paroxetine—overview of the molecular mechanisms of action. Int J Mol Sci. 2021 Feb;22(4):1662. doi:10.3390/ijms22041662.
Muñoz-Bellido JL, Muñoz-Criado S, García-Rodríguez JA. Antimicrobial activity of psychotropic drugs: selective serotonin reuptake inhibitors. Int J Antimicrob Agents. 2000 May;14(3):177–180. doi:10.1016/S0924-8579(99)00154-5.
National Committee for Clinical Laboratory Standards (NCCLS). Methods for determining bactericidal activity of antimicrobial agents. Wayne: NCCLS; 1999. Approved guideline M26-A.
Perez-Caballero L, et al. Fluoxetine: a case history of its discovery and preclinical development. Expert Opin Drug Discov. 2014 May;9(5):567–578. doi:10.1517/17460441.2014.907790.
Preda VG, Săndulescu O. Communication is the key: biofilms, quorum sensing, formation and prevention. Discoveries (Craiova). 2019;7(1):e91. doi:10.15190/d.2019.13.
Pushpakom S, et al. Drug repurposing: progress, challenges and recommendations. Nat Rev Drug Discov. 2019 Jan;18(1):41–58. doi:10.1038/nrd.2018.168.
Rodriguez-Tudela JL. EUCAST definitive document EDef 7.1: method for the determination of broth dilution MICs of antifungal agents for fermentative yeasts. Clin Microbiol Infect. 2008 Apr;14(4):398–405. doi:10.1111/j.1469-0691.2007.01935.x.
Rukavishnikov G, et al. Antimicrobial activity of antidepressants on normal gut microbiota: results of the in vitro study. Front Behav Neurosci. 2023;17:1132127. doi:10.3389/fnbeh.2023.1132127.
Smith K, et al. Influence of tigecycline on expression of virulence factors in biofilm-associated cells of methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 2010 Jan;54(1):380–387. doi:10.1128/AAC.00155-09.
Souza VA, Silva CM, Pimentel EF, et al. Antibacterial activity of duloxetine against multidrug-resistant bacteria. Microbial Pathogenesis. 2018;123:135–141. doi:10.1016/j.micpath.2018.07.040.
World Health Organization. Bacterial priority pathogens list: bacterial pathogens of public health importance to guide research, development and strategies to prevent and control antimicrobial resistance. Geneva: WHO; 2024.
Yin W, et al. Biofilms: the microbial “protective clothing” in extreme environments. Int J Mol Sci. 2019 Jul;20(14):3423. doi:10.3390/ijms20143423.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Giulianna Oliveira Lodetti, Luís Henrique Nunes de Souza, Liliana Scorzoni, Luiz Eduardo Nunes Ferreira, Priscila Luiza Mello
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
adopts the CC-BY-NC license for its publications, the copyright being held by the author, in cases of republication we recommend that authors indicate first publication in this journal.
This license allows you to copy and redistribute the material in any medium or format, remix, transform and develop the material, as long as it is not for commercial purposes. And due credit must be given to the creator.
The opinions expressed by the authors of the articles are their sole responsibility.
The magazine reserves the right to make normative, orthographic and grammatical changes to the originals in order to maintain the cultured standard of the language and the credibility of the vehicle. However, it will respect the writing style of the authors. Changes, corrections or suggestions of a conceptual nature will be sent to the authors when necessary.
This Journal is licensed with a license Creative Commons Assignment-NonCommercial 4.0 International.
