Repurposing Anti-diabetic Drugs to Cripple Quorum Sensing in <i>Pseudomonas aeruginosa</i>
<i>Pseudomonas aeruginosa</i> is a significant human pathogen, it possesses almost all of the known antimicrobial resistance mechanisms. Quorum sensing (QS) is an intercellular communication system that orchestrates bacterial virulence and its targeting is an effective approach to dimini...
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MDPI AG
2020-08-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/8/9/1285 |
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| author | Wael A. H. Hegazy Maan T. Khayat Tarek S. Ibrahim Majed S. Nassar Muhammed A. Bakhrebah Wesam H. Abdulaal Nabil A. Alhakamy Mahmoud M. Bendary |
| author_facet | Wael A. H. Hegazy Maan T. Khayat Tarek S. Ibrahim Majed S. Nassar Muhammed A. Bakhrebah Wesam H. Abdulaal Nabil A. Alhakamy Mahmoud M. Bendary |
| author_sort | Wael A. H. Hegazy |
| collection | DOAJ |
| description | <i>Pseudomonas aeruginosa</i> is a significant human pathogen, it possesses almost all of the known antimicrobial resistance mechanisms. Quorum sensing (QS) is an intercellular communication system that orchestrates bacterial virulence and its targeting is an effective approach to diminish its pathogenesis. Repurposing of drugs is an advantageous strategy, in this study we aimed to repurpose the anti-diabetic drugs sitagliptin, metformin and vildagliptin as anti-QS in <i>P. aeruginosa</i>. The effects of sub-inhibitory concentrations of the tested drugs on the expression of QS-encoding genes and QS-regulated virulence factors were assessed. The protective activity of tested drugs on <i>P. aeruginosa</i> pathogenesis was evaluated in vivo on mice. In silico analysis was performed to evaluate the interference capabilities of the tested drugs on QS-receptors. Although the three drugs reduced the expression of QS-encoding genes, only sitagliptin inhibited the <i>P. aeruginosa</i> virulence in vitro and protected mice from it. In contrast, metformin showed significant in vitro anti-QS activities but failed to protect mice from <i>P. aeruginosa</i>. Vildagliptin did not show any in vitro or in vivo efficacy. Sitagliptin is a promising anti-QS agent because of its chemical nature that hindered QS-receptors. Moreover, it gives an insight to consider their similar chemical structures as anti-QS agents or even design new chemically similar anti-QS pharmacophores. |
| first_indexed | 2024-03-10T16:59:20Z |
| format | Article |
| id | doaj.art-d104a60d08f54fc0b156fa3d003f0a2f |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-10T16:59:20Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-d104a60d08f54fc0b156fa3d003f0a2f2023-11-20T11:02:48ZengMDPI AGMicroorganisms2076-26072020-08-0189128510.3390/microorganisms8091285Repurposing Anti-diabetic Drugs to Cripple Quorum Sensing in <i>Pseudomonas aeruginosa</i>Wael A. H. Hegazy0Maan T. Khayat1Tarek S. Ibrahim2Majed S. Nassar3Muhammed A. Bakhrebah4Wesam H. Abdulaal5Nabil A. Alhakamy6Mahmoud M. Bendary7Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, EgyptDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaLife Science and Environment Research Institute, King Abdulaziz City for Science and Technology (KACST), P.O. Box 6086, Riyadh 11442, Saudi ArabiaLife Science and Environment Research Institute, King Abdulaziz City for Science and Technology (KACST), P.O. Box 6086, Riyadh 11442, Saudi ArabiaDepartment of Biochemistry, Cancer Metabolism and Epigenetic Unit, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi ArabiaCenter of Excellence for Drug Research & Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Microbiology and Immunology, Faculty of Pharmacy, Port Said University, Port Said 42526, Egypt<i>Pseudomonas aeruginosa</i> is a significant human pathogen, it possesses almost all of the known antimicrobial resistance mechanisms. Quorum sensing (QS) is an intercellular communication system that orchestrates bacterial virulence and its targeting is an effective approach to diminish its pathogenesis. Repurposing of drugs is an advantageous strategy, in this study we aimed to repurpose the anti-diabetic drugs sitagliptin, metformin and vildagliptin as anti-QS in <i>P. aeruginosa</i>. The effects of sub-inhibitory concentrations of the tested drugs on the expression of QS-encoding genes and QS-regulated virulence factors were assessed. The protective activity of tested drugs on <i>P. aeruginosa</i> pathogenesis was evaluated in vivo on mice. In silico analysis was performed to evaluate the interference capabilities of the tested drugs on QS-receptors. Although the three drugs reduced the expression of QS-encoding genes, only sitagliptin inhibited the <i>P. aeruginosa</i> virulence in vitro and protected mice from it. In contrast, metformin showed significant in vitro anti-QS activities but failed to protect mice from <i>P. aeruginosa</i>. Vildagliptin did not show any in vitro or in vivo efficacy. Sitagliptin is a promising anti-QS agent because of its chemical nature that hindered QS-receptors. Moreover, it gives an insight to consider their similar chemical structures as anti-QS agents or even design new chemically similar anti-QS pharmacophores.https://www.mdpi.com/2076-2607/8/9/1285<i>Pseudomonas aeruginosa</i>quorum sensingvirulencesitagliptinmetforminvildagliptin |
| spellingShingle | Wael A. H. Hegazy Maan T. Khayat Tarek S. Ibrahim Majed S. Nassar Muhammed A. Bakhrebah Wesam H. Abdulaal Nabil A. Alhakamy Mahmoud M. Bendary Repurposing Anti-diabetic Drugs to Cripple Quorum Sensing in <i>Pseudomonas aeruginosa</i> Microorganisms <i>Pseudomonas aeruginosa</i> quorum sensing virulence sitagliptin metformin vildagliptin |
| title | Repurposing Anti-diabetic Drugs to Cripple Quorum Sensing in <i>Pseudomonas aeruginosa</i> |
| title_full | Repurposing Anti-diabetic Drugs to Cripple Quorum Sensing in <i>Pseudomonas aeruginosa</i> |
| title_fullStr | Repurposing Anti-diabetic Drugs to Cripple Quorum Sensing in <i>Pseudomonas aeruginosa</i> |
| title_full_unstemmed | Repurposing Anti-diabetic Drugs to Cripple Quorum Sensing in <i>Pseudomonas aeruginosa</i> |
| title_short | Repurposing Anti-diabetic Drugs to Cripple Quorum Sensing in <i>Pseudomonas aeruginosa</i> |
| title_sort | repurposing anti diabetic drugs to cripple quorum sensing in i pseudomonas aeruginosa i |
| topic | <i>Pseudomonas aeruginosa</i> quorum sensing virulence sitagliptin metformin vildagliptin |
| url | https://www.mdpi.com/2076-2607/8/9/1285 |
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