Hiring of the Anti-Quorum Sensing Activities of Hypoglycemic Agent Linagliptin to Alleviate the <i>Pseudomonas aeruginosa</i> Pathogenesis
Bacteria communicate with each other using quorum sensing (QS) which works in an inducer/receptor manner. QS plays the main role in orchestrating diverse bacterial virulence factors. <i>Pseudomonas aeruginosa</i> is one of the most clinically important bacterial pathogens that can cause...
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MDPI AG
2022-12-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/10/12/2455 |
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| author | Maan T. Khayat Tarek S. Ibrahim Khaled M. Darwish Ahdab N. Khayyat Majed Alharbi El-Sayed Khafagy Mohamed A. M. Ali Wael A. H. Hegazy Hisham A. Abbas |
| author_facet | Maan T. Khayat Tarek S. Ibrahim Khaled M. Darwish Ahdab N. Khayyat Majed Alharbi El-Sayed Khafagy Mohamed A. M. Ali Wael A. H. Hegazy Hisham A. Abbas |
| author_sort | Maan T. Khayat |
| collection | DOAJ |
| description | Bacteria communicate with each other using quorum sensing (QS) which works in an inducer/receptor manner. QS plays the main role in orchestrating diverse bacterial virulence factors. <i>Pseudomonas aeruginosa</i> is one of the most clinically important bacterial pathogens that can cause infection in almost all body tissues. Besides its efficient capability to develop resistance to different antibiotics, <i>P. aeruginosa</i> acquires a huge arsenal of virulence factors that are controlled mainly by QS. Challenging QS with FDA-approved drugs and natural products was proposed as a promising approach to mitigate bacterial virulence enabling the host immunity to complete the eradication of bacterial infection. The present study aims to evaluate the dipeptidase inhibitor-4 inhibitor hypoglycemic linagliptin anti-QS and anti-virulence activities against <i>P. aeruginosa</i> in vitro, in vivo, and in silico. The current results revealed the significant ability to diminish the production of protease and pyocyanin, motility, and biofilm formation in <i>P. aeruginosa</i>. Furthermore, the histopathological examination of liver and kidney tissues of mice injected with linagliptin-treated bacteria showed an obvious reduction of pathogenesis. Linagliptin downregulation to QS-encoding genes, besides the virtual ability to interact with QS receptors, indicates its anti-QS activities. In conclusion, linagliptin is a promising anti-virulence and anti-QS candidate that can be used solely or in combination with traditional antimicrobial agents in the treatment of <i>P. aeruginosa</i> aggressive infections. |
| first_indexed | 2024-03-09T16:04:18Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-09T16:04:18Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-7d193628627f4fb590e21261ec832df72023-11-24T16:49:23ZengMDPI AGMicroorganisms2076-26072022-12-011012245510.3390/microorganisms10122455Hiring of the Anti-Quorum Sensing Activities of Hypoglycemic Agent Linagliptin to Alleviate the <i>Pseudomonas aeruginosa</i> PathogenesisMaan T. Khayat0Tarek S. Ibrahim1Khaled M. Darwish2Ahdab N. Khayyat3Majed Alharbi4El-Sayed Khafagy5Mohamed A. M. Ali6Wael A. H. Hegazy7Hisham A. Abbas8Department 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 ArabiaDepartment of Medicinal Chemistry, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, 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 ArabiaDepartment of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi ArabiaDepartment of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University, Riyadh 11432, Saudi ArabiaDepartment of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, EgyptDepartment of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, EgyptBacteria communicate with each other using quorum sensing (QS) which works in an inducer/receptor manner. QS plays the main role in orchestrating diverse bacterial virulence factors. <i>Pseudomonas aeruginosa</i> is one of the most clinically important bacterial pathogens that can cause infection in almost all body tissues. Besides its efficient capability to develop resistance to different antibiotics, <i>P. aeruginosa</i> acquires a huge arsenal of virulence factors that are controlled mainly by QS. Challenging QS with FDA-approved drugs and natural products was proposed as a promising approach to mitigate bacterial virulence enabling the host immunity to complete the eradication of bacterial infection. The present study aims to evaluate the dipeptidase inhibitor-4 inhibitor hypoglycemic linagliptin anti-QS and anti-virulence activities against <i>P. aeruginosa</i> in vitro, in vivo, and in silico. The current results revealed the significant ability to diminish the production of protease and pyocyanin, motility, and biofilm formation in <i>P. aeruginosa</i>. Furthermore, the histopathological examination of liver and kidney tissues of mice injected with linagliptin-treated bacteria showed an obvious reduction of pathogenesis. Linagliptin downregulation to QS-encoding genes, besides the virtual ability to interact with QS receptors, indicates its anti-QS activities. In conclusion, linagliptin is a promising anti-virulence and anti-QS candidate that can be used solely or in combination with traditional antimicrobial agents in the treatment of <i>P. aeruginosa</i> aggressive infections.https://www.mdpi.com/2076-2607/10/12/2455<i>Pseudomonas aeruginosa</i>linagliptinquorum sensingantimicrobial resistancebacterial virulencedrug repurposing |
| spellingShingle | Maan T. Khayat Tarek S. Ibrahim Khaled M. Darwish Ahdab N. Khayyat Majed Alharbi El-Sayed Khafagy Mohamed A. M. Ali Wael A. H. Hegazy Hisham A. Abbas Hiring of the Anti-Quorum Sensing Activities of Hypoglycemic Agent Linagliptin to Alleviate the <i>Pseudomonas aeruginosa</i> Pathogenesis Microorganisms <i>Pseudomonas aeruginosa</i> linagliptin quorum sensing antimicrobial resistance bacterial virulence drug repurposing |
| title | Hiring of the Anti-Quorum Sensing Activities of Hypoglycemic Agent Linagliptin to Alleviate the <i>Pseudomonas aeruginosa</i> Pathogenesis |
| title_full | Hiring of the Anti-Quorum Sensing Activities of Hypoglycemic Agent Linagliptin to Alleviate the <i>Pseudomonas aeruginosa</i> Pathogenesis |
| title_fullStr | Hiring of the Anti-Quorum Sensing Activities of Hypoglycemic Agent Linagliptin to Alleviate the <i>Pseudomonas aeruginosa</i> Pathogenesis |
| title_full_unstemmed | Hiring of the Anti-Quorum Sensing Activities of Hypoglycemic Agent Linagliptin to Alleviate the <i>Pseudomonas aeruginosa</i> Pathogenesis |
| title_short | Hiring of the Anti-Quorum Sensing Activities of Hypoglycemic Agent Linagliptin to Alleviate the <i>Pseudomonas aeruginosa</i> Pathogenesis |
| title_sort | hiring of the anti quorum sensing activities of hypoglycemic agent linagliptin to alleviate the i pseudomonas aeruginosa i pathogenesis |
| topic | <i>Pseudomonas aeruginosa</i> linagliptin quorum sensing antimicrobial resistance bacterial virulence drug repurposing |
| url | https://www.mdpi.com/2076-2607/10/12/2455 |
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