Repositioning of fluoxetine as anti-virulence agent against Pseudomonas aeruginosa
Abstract Background The bacterial resistance is an increasing obstacle against the global health that necessitates innovation of new approaches. Targeting bacterial resistance is one of the promising approaches. Pseudomonas aeruginosa is a clinically significant opportunistic pathogen and causes wid...
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| Format: | Article |
| Language: | English |
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SpringerOpen
2025-06-01
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| Series: | Future Journal of Pharmaceutical Sciences |
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| Online Access: | https://doi.org/10.1186/s43094-025-00833-3 |
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| author | Syed Mohd Danish Rizvi Amr Selim Abu Lila Afrasim Moin Shahanawaz Syed Daniya Fatima El-Sayed Khafagy Azza A. H. Rajab Wael A. H. Hegazy |
| author_facet | Syed Mohd Danish Rizvi Amr Selim Abu Lila Afrasim Moin Shahanawaz Syed Daniya Fatima El-Sayed Khafagy Azza A. H. Rajab Wael A. H. Hegazy |
| author_sort | Syed Mohd Danish Rizvi |
| collection | DOAJ |
| description | Abstract Background The bacterial resistance is an increasing obstacle against the global health that necessitates innovation of new approaches. Targeting bacterial resistance is one of the promising approaches. Pseudomonas aeruginosa is a clinically significant opportunistic pathogen and causes wide diverse of illness. The P. aeruginosa virulence is regulated by several systems as quorum sensing (QS) systems. Additionally, P. aeruginosa could employ membranal sensors to sense the neurotransmitters enhancing the virulence. Fluoxetine (FLU), an antidepressant, functions by inhibiting the reuptake of the neurotransmitter serotonin. This study aimed to assess the anti-virulence activity of FLU against P. aeruginosa. The effect of FLU at sub-inhibitory concentration was evaluated on the biofilm formation, removal of preformed biofilms, production of virulence factors such as protease, hemolysins, elastase, rhamnolipids, motility, pyocyanin, and pyoverdine. The impact of FLU on the expression of virulence-related genes was estimated. An invasion assay and mice protection assay were conducted to assess the FLU’s diminishing effect on P. aeruginosa pathogenesis. Results The results showed significant ability of FLU to inhibit the biofilm formation, bacterial motility, and production of virulence factors. These antibiofilm and anti-virulence activities of FLU were owed to the downregulation of genes involved in expression of QS systems and bacterial espionage. FLU significantly lowered the bacterial invasion and protected mice from P. aeruginosa. Additionally, synergistic outcome was obtained when FLU was combined with antibiotics. Conclusion FLU exhibits potent antibiofilm and anti-virulence effects at sub-MIC levels, likely mediated by its inhibition of QS systems. These results position FLU as a promising candidate for adjuvant therapy against drug-resistant P. aeruginosa infections. |
| format | Article |
| id | doaj-art-2b7f58d9d33a4316a87417826cbea55e |
| institution | Kabale University |
| issn | 2314-7253 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Future Journal of Pharmaceutical Sciences |
| spelling | doaj-art-2b7f58d9d33a4316a87417826cbea55e2025-08-20T03:31:44ZengSpringerOpenFuture Journal of Pharmaceutical Sciences2314-72532025-06-0111111410.1186/s43094-025-00833-3Repositioning of fluoxetine as anti-virulence agent against Pseudomonas aeruginosaSyed Mohd Danish Rizvi0Amr Selim Abu Lila1Afrasim Moin2Shahanawaz Syed3Daniya Fatima4El-Sayed Khafagy5Azza A. H. Rajab6Wael A. H. Hegazy7Department of Pharmaceutics, College of Pharmacy, University of Ha’ilDepartment of Pharmaceutics, College of Pharmacy, University of Ha’ilDepartment of Pharmaceutics, College of Pharmacy, University of Ha’ilDepartment of Physical Therapy, College of Applied Medical Sciences, University of Ha’ilDepartment of Public Health, College of Public Health and Health Informatics, University of Ha’ilDepartment of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz UniversityDepartment of Microbiology and Immunology, Faculty of Pharmacy, Zagazig UniversityDepartment of Microbiology and Immunology, Faculty of Pharmacy, Zagazig UniversityAbstract Background The bacterial resistance is an increasing obstacle against the global health that necessitates innovation of new approaches. Targeting bacterial resistance is one of the promising approaches. Pseudomonas aeruginosa is a clinically significant opportunistic pathogen and causes wide diverse of illness. The P. aeruginosa virulence is regulated by several systems as quorum sensing (QS) systems. Additionally, P. aeruginosa could employ membranal sensors to sense the neurotransmitters enhancing the virulence. Fluoxetine (FLU), an antidepressant, functions by inhibiting the reuptake of the neurotransmitter serotonin. This study aimed to assess the anti-virulence activity of FLU against P. aeruginosa. The effect of FLU at sub-inhibitory concentration was evaluated on the biofilm formation, removal of preformed biofilms, production of virulence factors such as protease, hemolysins, elastase, rhamnolipids, motility, pyocyanin, and pyoverdine. The impact of FLU on the expression of virulence-related genes was estimated. An invasion assay and mice protection assay were conducted to assess the FLU’s diminishing effect on P. aeruginosa pathogenesis. Results The results showed significant ability of FLU to inhibit the biofilm formation, bacterial motility, and production of virulence factors. These antibiofilm and anti-virulence activities of FLU were owed to the downregulation of genes involved in expression of QS systems and bacterial espionage. FLU significantly lowered the bacterial invasion and protected mice from P. aeruginosa. Additionally, synergistic outcome was obtained when FLU was combined with antibiotics. Conclusion FLU exhibits potent antibiofilm and anti-virulence effects at sub-MIC levels, likely mediated by its inhibition of QS systems. These results position FLU as a promising candidate for adjuvant therapy against drug-resistant P. aeruginosa infections.https://doi.org/10.1186/s43094-025-00833-3FluoxetinePseudomonas aeruginosaAntibiofilmAnti-virulenceQuorum sensingBacterial espionage |
| spellingShingle | Syed Mohd Danish Rizvi Amr Selim Abu Lila Afrasim Moin Shahanawaz Syed Daniya Fatima El-Sayed Khafagy Azza A. H. Rajab Wael A. H. Hegazy Repositioning of fluoxetine as anti-virulence agent against Pseudomonas aeruginosa Future Journal of Pharmaceutical Sciences Fluoxetine Pseudomonas aeruginosa Antibiofilm Anti-virulence Quorum sensing Bacterial espionage |
| title | Repositioning of fluoxetine as anti-virulence agent against Pseudomonas aeruginosa |
| title_full | Repositioning of fluoxetine as anti-virulence agent against Pseudomonas aeruginosa |
| title_fullStr | Repositioning of fluoxetine as anti-virulence agent against Pseudomonas aeruginosa |
| title_full_unstemmed | Repositioning of fluoxetine as anti-virulence agent against Pseudomonas aeruginosa |
| title_short | Repositioning of fluoxetine as anti-virulence agent against Pseudomonas aeruginosa |
| title_sort | repositioning of fluoxetine as anti virulence agent against pseudomonas aeruginosa |
| topic | Fluoxetine Pseudomonas aeruginosa Antibiofilm Anti-virulence Quorum sensing Bacterial espionage |
| url | https://doi.org/10.1186/s43094-025-00833-3 |
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