Selective Serotonin Reuptake Inhibitors: Antimicrobial Activity Against ESKAPEE Bacteria and Mechanisms of Action
<b>Background:</b> Multidrug-resistant bacteria cause over 700,000 deaths annually, a figure projected to reach 10 million by 2050. Among these bacteria, the ESKAPEE group is notable for its multiple resistance mechanisms. Given the high costs of developing new antimicrobials and the rap...
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2025-01-01
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| author | Thiago Hideo Endo Mariana Homem de Mello Santos Sara Scandorieiro Bruna Carolina Gonçalves Eliana Carolina Vespero Márcia Regina Eches Perugini Wander Rogério Pavanelli Gerson Nakazato Renata Katsuko Takayama Kobayashi |
| author_facet | Thiago Hideo Endo Mariana Homem de Mello Santos Sara Scandorieiro Bruna Carolina Gonçalves Eliana Carolina Vespero Márcia Regina Eches Perugini Wander Rogério Pavanelli Gerson Nakazato Renata Katsuko Takayama Kobayashi |
| author_sort | Thiago Hideo Endo |
| collection | DOAJ |
| description | <b>Background:</b> Multidrug-resistant bacteria cause over 700,000 deaths annually, a figure projected to reach 10 million by 2050. Among these bacteria, the ESKAPEE group is notable for its multiple resistance mechanisms. Given the high costs of developing new antimicrobials and the rapid emergence of resistance, drug repositioning offers a promising alternative. <b>Results:</b> This study evaluates the antibacterial activity of sertraline and paroxetine. When tested against clinical and reference strains from the ESKAPEE group, sertraline exhibited minimum inhibitory concentration (MIC) values between 15 and 126 μg/mL, while the MIC values for paroxetine ranged from 60 to 250 μg/mL. Both drugs effectively eradicated bacterial populations within 2 to 24 h and caused morphological changes, such as protrusions and cellular fragmentation, as shown by electron scanning microscopy. Regarding their mechanisms of action as antibacterials, for the first time, increased membrane permeability was detected, as evidenced by heightened dye absorption, along with the increased presence of total proteins and dsDNA in the extracellular medium of <i>Escherichia coli</i> ATCC2 25922 and <i>Staphylococcus aureus</i> ATCC 25923, and oxidative stress was also detected in bacteria treated with sertraline and paroxetine, with reduced efficiency observed in the presence of antioxidants and higher levels of oxygen-reactive species evidenced by their reaction with 6-carboxy-2′,7′-dichlorodihydrofluorescein diacetate. The drugs also inhibited bacterial efflux pumps, increasing ethidium bromide accumulation and enhancing tetracycline activity in resistant strains. <b>Conclusions:</b> These findings indicate that sertraline and paroxetine could serve as alternative treatments against multidrug-resistant bacteria, as well as efflux pump inhibitors (EPIs), and they support further development of antimicrobial agents based on these compounds. |
| format | Article |
| id | doaj-art-a7517e0150e24098b95526fe3a0ea1bd |
| institution | Kabale University |
| issn | 2079-6382 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| series | Antibiotics |
| spelling | doaj-art-a7517e0150e24098b95526fe3a0ea1bd2025-01-24T13:18:44ZengMDPI AGAntibiotics2079-63822025-01-011415110.3390/antibiotics14010051Selective Serotonin Reuptake Inhibitors: Antimicrobial Activity Against ESKAPEE Bacteria and Mechanisms of ActionThiago Hideo Endo0Mariana Homem de Mello Santos1Sara Scandorieiro2Bruna Carolina Gonçalves3Eliana Carolina Vespero4Márcia Regina Eches Perugini5Wander Rogério Pavanelli6Gerson Nakazato7Renata Katsuko Takayama Kobayashi8Laboratory of Basic and Applied Bacteriology, Department of Microbiology, Center of Biological Sciences, Universidade Estadual de Londrina, Londrina 86057-970, BrazilLaboratory of Basic and Applied Bacteriology, Department of Microbiology, Center of Biological Sciences, Universidade Estadual de Londrina, Londrina 86057-970, BrazilLaboratory of Innovation and Cosmeceutical Technology, Department of Pharmaceutical Sciences, Center of Health Sciences, Hospital Universitário de Londrina, Londrina 86038-350, BrazilLaboratory of Basic and Applied Bacteriology, Department of Microbiology, Center of Biological Sciences, Universidade Estadual de Londrina, Londrina 86057-970, BrazilLaboratory of Clinical Analysis Microbiology Sector, Department of Pathology, Clinical and Toxicological Analysis, Center of Health Sciences, Hospital Universitário de Londrina, Londrina 86038-350, BrazilLaboratory of Clinical Analysis Microbiology Sector, Department of Pathology, Clinical and Toxicological Analysis, Center of Health Sciences, Hospital Universitário de Londrina, Londrina 86038-350, BrazilLaboratory of Experimental Protozoology, Department of Pathological Sciences, Center of Biological Sciences, Universidade Estadual de Londrina, Londrina 86057-970, BrazilLaboratory of Basic and Applied Bacteriology, Department of Microbiology, Center of Biological Sciences, Universidade Estadual de Londrina, Londrina 86057-970, BrazilLaboratory of Basic and Applied Bacteriology, Department of Microbiology, Center of Biological Sciences, Universidade Estadual de Londrina, Londrina 86057-970, Brazil<b>Background:</b> Multidrug-resistant bacteria cause over 700,000 deaths annually, a figure projected to reach 10 million by 2050. Among these bacteria, the ESKAPEE group is notable for its multiple resistance mechanisms. Given the high costs of developing new antimicrobials and the rapid emergence of resistance, drug repositioning offers a promising alternative. <b>Results:</b> This study evaluates the antibacterial activity of sertraline and paroxetine. When tested against clinical and reference strains from the ESKAPEE group, sertraline exhibited minimum inhibitory concentration (MIC) values between 15 and 126 μg/mL, while the MIC values for paroxetine ranged from 60 to 250 μg/mL. Both drugs effectively eradicated bacterial populations within 2 to 24 h and caused morphological changes, such as protrusions and cellular fragmentation, as shown by electron scanning microscopy. Regarding their mechanisms of action as antibacterials, for the first time, increased membrane permeability was detected, as evidenced by heightened dye absorption, along with the increased presence of total proteins and dsDNA in the extracellular medium of <i>Escherichia coli</i> ATCC2 25922 and <i>Staphylococcus aureus</i> ATCC 25923, and oxidative stress was also detected in bacteria treated with sertraline and paroxetine, with reduced efficiency observed in the presence of antioxidants and higher levels of oxygen-reactive species evidenced by their reaction with 6-carboxy-2′,7′-dichlorodihydrofluorescein diacetate. The drugs also inhibited bacterial efflux pumps, increasing ethidium bromide accumulation and enhancing tetracycline activity in resistant strains. <b>Conclusions:</b> These findings indicate that sertraline and paroxetine could serve as alternative treatments against multidrug-resistant bacteria, as well as efflux pump inhibitors (EPIs), and they support further development of antimicrobial agents based on these compounds.https://www.mdpi.com/2079-6382/14/1/51SSRIdrug repositioningefflux pump inhibitorsoxidative stressmultidrug resistance |
| spellingShingle | Thiago Hideo Endo Mariana Homem de Mello Santos Sara Scandorieiro Bruna Carolina Gonçalves Eliana Carolina Vespero Márcia Regina Eches Perugini Wander Rogério Pavanelli Gerson Nakazato Renata Katsuko Takayama Kobayashi Selective Serotonin Reuptake Inhibitors: Antimicrobial Activity Against ESKAPEE Bacteria and Mechanisms of Action Antibiotics SSRI drug repositioning efflux pump inhibitors oxidative stress multidrug resistance |
| title | Selective Serotonin Reuptake Inhibitors: Antimicrobial Activity Against ESKAPEE Bacteria and Mechanisms of Action |
| title_full | Selective Serotonin Reuptake Inhibitors: Antimicrobial Activity Against ESKAPEE Bacteria and Mechanisms of Action |
| title_fullStr | Selective Serotonin Reuptake Inhibitors: Antimicrobial Activity Against ESKAPEE Bacteria and Mechanisms of Action |
| title_full_unstemmed | Selective Serotonin Reuptake Inhibitors: Antimicrobial Activity Against ESKAPEE Bacteria and Mechanisms of Action |
| title_short | Selective Serotonin Reuptake Inhibitors: Antimicrobial Activity Against ESKAPEE Bacteria and Mechanisms of Action |
| title_sort | selective serotonin reuptake inhibitors antimicrobial activity against eskapee bacteria and mechanisms of action |
| topic | SSRI drug repositioning efflux pump inhibitors oxidative stress multidrug resistance |
| url | https://www.mdpi.com/2079-6382/14/1/51 |
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