Antibacterial activity of paroxetine against Staphylococcus aureus and possible mechanisms of action

Vitória Pf Cabral1,2, Daniel S Rodrigues1,2, Amanda D Barbosa1,2

  • 1Faculdade de Farmácia, Laboratório de Bioprospecção em Moléculas Antimicrobianas (LABIMAN), Universidade Federal do Ceará, Fortaleza, CE, CEP: 60.430-372, Brasil.

Future Microbiology
|May 22, 2023
PubMed

Insights

Paroxetine exhibits antibacterial potential, showing additive effects with oxacillin against Staphylococcus aureus. This antidepressant may be repurposed as a novel antibacterial agent.

Area of Science:

  • Pharmacology
  • Microbiology
  • Drug Discovery

Background:

  • Staphylococcus aureus infections pose a significant public health threat, necessitating novel therapeutic strategies.
  • Antibiotic resistance in S. aureus strains, including methicillin-resistant Staphylococcus aureus (MRSA), complicates treatment options.
  • Drug repositioning offers a promising avenue for identifying new uses for existing medications.

Purpose of the Study:

  • To investigate the antibacterial activity of paroxetine, an antidepressant, against methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MRSA) isolates.
  • To evaluate the synergistic or additive effects of combining paroxetine with oxacillin, a beta-lactam antibiotic.
  • To explore the potential mechanisms of action underlying paroxetine's antibacterial effects.

Main Methods:

  • Broth microdilution and checkerboard assays were employed to determine minimum inhibitory concentrations (MIC) and fractional inhibitory concentration indices.
  • Flow cytometry and fluorescence microscopy were utilized to assess effects on bacterial genetic material and cell membranes.
  • Scanning electron microscopy (SEM) was used for morphological analysis of bacterial cells treated with paroxetine.
  • Molecular docking studies were performed to predict interactions with potential bacterial targets.

Main Results:

  • Paroxetine demonstrated a minimum inhibitory concentration (MIC) of 64 μg/ml against Staphylococcus aureus.
  • The combination of paroxetine and oxacillin exhibited mostly additive interactions, suggesting a potential synergistic effect.
  • Evidence indicated that paroxetine affects bacterial genetic material and cell membranes, leading to morphological changes and influencing virulence factors.

Conclusions:

  • Paroxetine possesses significant antibacterial potential, particularly against Staphylococcus aureus.
  • The findings support the drug repositioning of paroxetine as a potential therapeutic agent for bacterial infections.
  • Further research into the precise mechanisms and clinical efficacy of paroxetine as an antibacterial is warranted.

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