The antidepressants effect on the opportunistic microorganisms virulence



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Abstract

Introduction. The increasing use of antidepressants in clinical practice determines relevance of investigating their related "side" effect spectrum on opportunistic pathogens. Apart from modulating human neurotransmitter cascades, antidepressants markedly affect intestinal microbiota, however, such impact has not been fully assessed. Aim. Investigating an effect of antidepressants on virulence of opportunistic microorganisms. Materials and methods. The study examined clinical isolates of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus. Bacterial biomass accumulation and polysaccharide matrix (biofilm formation) production as well as the rate of adhesion and metabolic activity upon exposure to main antidepressant groups were evaluated. The studied drugs were as follows: selective serotonin reuptake inhibitors (fluoxetine, sertaline), a serotonin and norepinephrine reuptake inhibitor (venflaxine), and a tricyclic antidepressant (amitriptyline) that inhibits monoamines neuronal reuptake. To assess formation of biomass and extracellular matrix, gentian purple and Congo red staining, respectively, were carried out. Bacterial adhesion was assessed following 30 minutes, 1h, 2h, 3h and 6 hours post-exposure. The metabolic activity was assessed by using colorimetric MTT test. Results. Antidepressants have a differentiated effect on bacterial growth and biofilm formation. In particular, fluoxetine significantly stimulated E. coli replication while reducing matrix synthesis. Venlafaxine accelerated P. aeruginosa replication and activated matrix production in S. aureus. Amitriptyline activated the growth of both P. aeruginosa and S. aureus; however, matrix production remained unchanged. Zoloft (sertalin) significantly reduced matrix production in E.coli and activated matrix synthesis in S. aureus. Fluoxetine, amitriptyline and venlafaxine had a significant effect on E.coli adhesion. Increased metabolic activity was noted for P. aeruginosa and E. coli exposed to the studied antidepressants, amitriptyline also activated K.pneumoniae. Conclusion. Thus, antidepressants can have a "side effect" on opportunistic pathogens virulence. Stimulation of replication of specific bacterial members can cause dysbiosis, and activation of adhesion, whereas biofilm formation may result in chronic course of infectious process. Altogether, the findings presented here highlight a need to further seek out for means for lowering risks associated with antidepressant intake.

About the authors

Nadezhda Ignatova

Privolzhsky Research Medical University, Nizhny Novgorod, Russia

Email: n.i.evteeva@gmail.com
ORCID iD: 0000-0002-4570-9342

Associate Professor of the Department of Epidemiology, Microbiology and Evidence-based Medicine

Russian Federation, 603950, Russia, Bld. 10/1, Minin and Pozharsky Square, Nizhny Novgorod

Kira Yurievna Guzenok

National Research Lobachevsky State University of Nizhny Novgorod, Institute of Biology and Biomedicine, Nizhny Novgorod, Russia

Email: guzenkkiroch@gmail.com

student

Russian Federation, 603022, Russia, 23 Gagarin Ave., Nizhny Novgorod

Maxim Sergeevich Birin

National Research Lobachevsky State University of Nizhny Novgorod, Institute of Biology and Biomedicine, Nizhny Novgorod, Russia

Email: m.poluchowicz@yandex.ru
ORCID iD: 0009-0001-8161-3989

student

Russian Federation, 603022, Russia, 23 Gagarin Ave., Nizhny Novgorod

Alina Abdulkhadirovna Abidullina

Privolzhsky Research Medical University, Nizhny Novgorod, Russia

Author for correspondence.
Email: lina.abidullina@yandex.ru
ORCID iD: 0000-0002-8981-7492

the resident

Russian Federation, 603950, Russia, Bld. 10/1, Minin and Pozharsky Square, Nizhny Novgorod,

References

  1. Догузова В. Пик продаж антидепрессантов за 10 лет пришелся на 2023 год // Фармацевтический вестник. 2024. Doguzova V. The peak of sales of antidepressants in 10 years occurred in 2023 // Pharmaceutical Bulletin. 2024. https://pharmvestnik.ru/content/news/Pik-prodaj-antidepressantov-za-10-let-prishelsya-na-2023-god.html
  2. Незнанов Н. Г., Мазуркевич А. В., Крылов В. И. Микробиота кишечника как объект для изучения при психических расстройствах // Успехи физиологических наук. 2021. Т. 52. № 1. С. 64–76. Neznanov N. G., Mazurkevich A.V., Krylov V. I. Intestinal microbiota as an object for study in mental disorders // Successes of physiological sciences. 2021. Vol. 52. No. 1. pp. 64-76. https://doi.org/10.31857/S0301179821010069.
  3. Ait Chait Y., Mottawea W., Tompkins T. A., Hammami R. Unravelling the antimicrobial action of antidepressants on gut commensal microbes // Scientific Reports. 2020. Vol. 10. р. 17878. https://doi.org/10.1038/s41598-020-74934-9.
  4. Arrieta-Ortiz ML, Pan M, Kaur A, Pepper-Tunick E, Srinivas V, Dash A, Immanuel SRC, Brooks AN, Shepherd TR, Baliga NS. Disrupting the ArcA Regulatory Network Amplifies the Fitness Cost of Tetracycline Resistance in Escherichia coli // mSystems. 2023 Feb 23;8(1):e0090422. https://doi.org/10.1128/msystems.00904-22.
  5. Caldara M, Marmiroli N. Antimicrobial Properties of Antidepressants and Antipsychotics-Possibilities and Implications // Pharmaceuticals (Basel). 2021 Sep 10;14(9):915. https://doi.org/10.3390/ph14090915.
  6. Cussotto S., Strain C. R., Fouhy F. et al. Differential effects of psychotropic drugs on microbiome composition and gastrointestinal function // Psychopharmacology. 2019. Vol. 236. рр. 1671–1685. https://doi.org/10.1007/s00213-018-5006-5.
  7. Guo J. et al. Antidepressants as a driver of antibiotic resistance: Mechanisms and clinical implications // mBio. 2022. Vol. 13. e02191-22. https://doi.org/10.1128/mbio.02191-22.
  8. Mohiuddin SG, Ghosh S, Kavousi P, Orman MA. Proton Motive Force Inhibitors Are Detrimental to Methicillin-Resistant Staphylococcus aureus Strains // Microbiol Spectr. 2022 Aug 31;10(4):e0202422. https://doi.org/10.1128/spectrum.02024-22.
  9. Ninomiya K, Paudel D, Uehara O, Morikawa T, Islam ST, Khurelchuluun A, Ariwansa D, Yoshida K, Matsuoka H, Hajime H, Kayoko F, Nakamura K, Abiko Y. Effect of Systemic Administration of Amitriptyline on Oral Microbes in Rats // In Vivo. 2022 Sep-Oct;36(5):2134-2142. https://doi.org/10.21873/invivo.12939.
  10. Ou J., Elizalde P., Guo H. B. et al. TCA and SSRI antidepressants exert selection pressure for efflux-dependent antibiotic resistance mechanisms in Escherichia coli // mBio. 2022. Vol. 13. e02191-22. https://doi.org/10.1128/mbio.02191-22.
  11. Rukavishnikov G., Leonova L., Kasyanov E. et al. Antimicrobial activity of antidepressants on normal gut microbiota: Results of the in vitro study // Frontiers in Behavioral Neuroscience. 2023. Vol. 17. р. 1132127. https://doi.org/10.3389/fnbeh.2023.1132127.
  12. Simpson C. A., Diaz-Arteche C., Eliby D. et al. The gut microbiota in anxiety and depression – A systematic review // Clinical Psychology Review. 2021. Vol. 83. р. 101943. https://doi.org/10.1016/j.cpr.2020.101943.
  13. Suna Sibel Gurpinar, Didem Kart, Mujde Eryilmaz The efects of antidepressants fuoxetine, sertraline, and amitriptyline on the development of antibiotic resistance in Acinetobacter baumannii // Archives of Microbiology. 2022. 204:230 https://doi.org/10.1007/s00203-022-02853-6
  14. Tien T.T. Do, Uyen P.N. Dao, Huong T. Bui, Trang T. Nguyen Effect of electrostatic interaction between fluoxetine and lipid membranes on the partitioning of fluoxetine investigated using second derivative spectrophotometry and FTIR // Chemistry and Physics of Lipids, Vol. 207, Part A, 2017, рр. 10-3. https://doi.org/10.1016/j.chemphyslip.2017.07.001.
  15. Tiwana, Gagan, Ian Edwin Cock, Stephen Maxwell Taylor, and Matthew James Cheesman Beyond Antibiotics: Repurposing Non-Antibiotic Drugs as Novel Antibacterial Agents to Combat Resistance // International Journal of Molecular Sciences. 2025.26, No. 20: 9880. https://doi.org/10.3390/ijms26209880

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