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Improved Enzyme Protection Assay to Study Staphylococcus aureus Internalization and Intracellular Efficacy of Antimicrobial Compounds
Published on: September 8, 2021
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.
Abstract:
Aim: To evaluate the antibacterial activity of paroxetine alone and associated with oxacillin against isolates of methicillin-sensitive and -resistant Staphylococcus aureus. Materials & methods: The broth microdilution and checkerboard techniques were used, with investigation of possible mechanisms of action through flow cytometry, fluorescence microscopy and molecular docking, in addition to scanning electron microscopy for morphological analysis. Results: Paroxetine showed a MIC of 64 μg/ml and bactericidal activity, mostly additive interactions in combination with oxacillin, evidence of action on genetic material and membrane, morphological changes in microbial cells and influence on virulence factors. Conclusion: Paroxetine has antibacterial potential from the perspective of drug repositioning.
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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