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<p>Antimicrobial resistance in <i>Escherichia coli</i> strains producing extended-spectrum beta-lactamases is a growing global health concern, compounded by the shortage of new antibiotics. Drug repositioning offers a promising alternative, and selective serotonin reuptake inhibitors have recently shown unexpected antibacterial properties. This study evaluated the <i>in vitro</i> antibacterial activity of sertraline, paroxetine, and fluoxetine against extended-spectrum beta-lactamase-producing <i>Escherichia coli</i>, their interactions with ciprofloxacin and meropenem, and their mechanisms of action. Antibacterial activity was assessed by the broth microdilution method, and drug interactions were evaluated using the checkerboard assay. Flow cytometry and fluorescence microscopy were employed to investigate reactive oxygen species generation and DNA damage. The tested compounds exhibited <i>in vitro</i> antibacterial activity, with minimum inhibitory concentrations ranging from 64 to 426.7 μg/mL. Combinations with ciprofloxacin or meropenem showed indifferent effects. Mechanistic analyses revealed that the antidepressants increased reactive oxygen species production and induced DNA damage, leading to apoptosis-like bacterial cell death and a significant reduction in viability. These findings demonstrate that sertraline, paroxetine, and fluoxetine have antibacterial activity against extended-spectrum beta-lactamase-producing <i>Escherichia coli</i> and induce cell death via oxidative stress and genomic damage. Although no synergistic interaction was observed with conventional antibiotics, the data support the potential of these compounds as adjuvants in the treatment of infections caused by multidrug-resistant <i>Escherichia coli</i>.</p>

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Antibacterial potential of antidepressants against extended-spectrum β-lactamase-producing Escherichia coli

  • 期刊论文

  • 发表日期：

    2025年9月15日

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  • Cecília Rocha da Silva,
  • Lívia Gurgel do Amaral Valente Sá,
  • Vitória Pessoa de Farias Cabral,
  • Daniel Sampaio Rodrigues,
  • Lara Elloyse Almeida Moreira,
  • Érica Rayanne Mota da Costa,
  • Thais Lima Ferreira,
  • Maria Janielly Castelo Branco Silveira,
  • Tatiana do Nascimento Paiva Coutinho,
  • Letícia Bernardo Barbosa,
  • Igor Gomes Aguiar,
  • Bruno Coêlho Cavalcanti,
  • Amanda Cavalcante Leitão,
  • Manoel Odorico de Moraes,
  • Hélio Vitoriano Nobre Júnior,
  • João Batista de Andrade Neto

摘要

Antimicrobial resistance in Escherichia coli strains producing extended-spectrum beta-lactamases is a growing global health concern, compounded by the shortage of new antibiotics. Drug repositioning offers a promising alternative, and selective serotonin reuptake inhibitors have recently shown unexpected antibacterial properties. This study evaluated the in vitro antibacterial activity of sertraline, paroxetine, and fluoxetine against extended-spectrum beta-lactamase-producing Escherichia coli, their interactions with ciprofloxacin and meropenem, and their mechanisms of action. Antibacterial activity was assessed by the broth microdilution method, and drug interactions were evaluated using the checkerboard assay. Flow cytometry and fluorescence microscopy were employed to investigate reactive oxygen species generation and DNA damage. The tested compounds exhibited in vitro antibacterial activity, with minimum inhibitory concentrations ranging from 64 to 426.7 μg/mL. Combinations with ciprofloxacin or meropenem showed indifferent effects. Mechanistic analyses revealed that the antidepressants increased reactive oxygen species production and induced DNA damage, leading to apoptosis-like bacterial cell death and a significant reduction in viability. These findings demonstrate that sertraline, paroxetine, and fluoxetine have antibacterial activity against extended-spectrum beta-lactamase-producing Escherichia coli and induce cell death via oxidative stress and genomic damage. Although no synergistic interaction was observed with conventional antibiotics, the data support the potential of these compounds as adjuvants in the treatment of infections caused by multidrug-resistant Escherichia coli.