A Novel Use of Allopurinol as A Quorum-Sensing Inhibitor in <i>Pseudomonas aeruginosa</i>
<i>Pseudomonas aeruginosa</i> can cause a variety of healthcare-associated infections by its arsenal of virulence factors. Virulence factor production is largely controlled by the cell-to-cell communication system termed quorum sensing (QS). Targeting QS may be a good approach to inhibit...
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| Format: | Article |
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MDPI AG
2021-11-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/10/11/1385 |
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| author | Ahmed Al Saqr Mohammed F. Aldawsari El-Sayed Khafagy Moataz A. Shaldam Wael A. H. Hegazy Hisham A. Abbas |
| author_facet | Ahmed Al Saqr Mohammed F. Aldawsari El-Sayed Khafagy Moataz A. Shaldam Wael A. H. Hegazy Hisham A. Abbas |
| author_sort | Ahmed Al Saqr |
| collection | DOAJ |
| description | <i>Pseudomonas aeruginosa</i> can cause a variety of healthcare-associated infections by its arsenal of virulence factors. Virulence factor production is largely controlled by the cell-to-cell communication system termed quorum sensing (QS). Targeting QS may be a good approach to inhibit the production of virulence factors and attenuate pathogenicity without exerting selective stress on bacterial growth. This will greatly reduce the emergence of resistant mutants. In this work, we investigated the anti-virulence and anti-QS activities of the FDA-approved drug allopurinol against the <i>P. aeruginosa</i> PAO1 strain. Allopurinol at 200 µg/mL (1/10 MIC) significantly decreased the production of the QS-controlled <i>Chromobacterium violaceum</i> CV026 violet pigment violacein and other <i>P. aeruginosa</i> QS-controlled virulence factors phenotypically. Furthermore, allopurinol reduced the infiltration of <i>P. aeruginosa</i> and leucocytes and diminished the congestion in the liver and kidney tissues of infected mice. In silico study showed that allopurinol could compete with the autoinducers on binding to the receptors LasR and RhlR by hydrogen bonding. On the molecular level, qRT-PCR proved that allopurinol showed a significant downregulating effect on all tested QS-encoding genes that regulate virulence factor production. In summary, allopurinol is a promising QS inhibitor that may be useful in the future treatment of <i>P. aeruginosa</i> infection. |
| first_indexed | 2024-03-10T05:45:36Z |
| format | Article |
| id | doaj.art-d4c4d2fcd7af4ca2aaa8edb7d474e510 |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-10T05:45:36Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-d4c4d2fcd7af4ca2aaa8edb7d474e5102023-11-22T22:10:52ZengMDPI AGAntibiotics2079-63822021-11-011011138510.3390/antibiotics10111385A Novel Use of Allopurinol as A Quorum-Sensing Inhibitor in <i>Pseudomonas aeruginosa</i>Ahmed Al Saqr0Mohammed F. Aldawsari1El-Sayed Khafagy2Moataz A. Shaldam3Wael A. H. Hegazy4Hisham A. Abbas5Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-kharj 11942, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-kharj 11942, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-kharj 11942, Saudi ArabiaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafr El-Sheikh 33511, EgyptDepartment of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, EgyptDepartment of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt<i>Pseudomonas aeruginosa</i> can cause a variety of healthcare-associated infections by its arsenal of virulence factors. Virulence factor production is largely controlled by the cell-to-cell communication system termed quorum sensing (QS). Targeting QS may be a good approach to inhibit the production of virulence factors and attenuate pathogenicity without exerting selective stress on bacterial growth. This will greatly reduce the emergence of resistant mutants. In this work, we investigated the anti-virulence and anti-QS activities of the FDA-approved drug allopurinol against the <i>P. aeruginosa</i> PAO1 strain. Allopurinol at 200 µg/mL (1/10 MIC) significantly decreased the production of the QS-controlled <i>Chromobacterium violaceum</i> CV026 violet pigment violacein and other <i>P. aeruginosa</i> QS-controlled virulence factors phenotypically. Furthermore, allopurinol reduced the infiltration of <i>P. aeruginosa</i> and leucocytes and diminished the congestion in the liver and kidney tissues of infected mice. In silico study showed that allopurinol could compete with the autoinducers on binding to the receptors LasR and RhlR by hydrogen bonding. On the molecular level, qRT-PCR proved that allopurinol showed a significant downregulating effect on all tested QS-encoding genes that regulate virulence factor production. In summary, allopurinol is a promising QS inhibitor that may be useful in the future treatment of <i>P. aeruginosa</i> infection.https://www.mdpi.com/2079-6382/10/11/1385quorum sensingallopurinolvirulence inhibition<i>Pseudomonas aeruginosa</i> |
| spellingShingle | Ahmed Al Saqr Mohammed F. Aldawsari El-Sayed Khafagy Moataz A. Shaldam Wael A. H. Hegazy Hisham A. Abbas A Novel Use of Allopurinol as A Quorum-Sensing Inhibitor in <i>Pseudomonas aeruginosa</i> Antibiotics quorum sensing allopurinol virulence inhibition <i>Pseudomonas aeruginosa</i> |
| title | A Novel Use of Allopurinol as A Quorum-Sensing Inhibitor in <i>Pseudomonas aeruginosa</i> |
| title_full | A Novel Use of Allopurinol as A Quorum-Sensing Inhibitor in <i>Pseudomonas aeruginosa</i> |
| title_fullStr | A Novel Use of Allopurinol as A Quorum-Sensing Inhibitor in <i>Pseudomonas aeruginosa</i> |
| title_full_unstemmed | A Novel Use of Allopurinol as A Quorum-Sensing Inhibitor in <i>Pseudomonas aeruginosa</i> |
| title_short | A Novel Use of Allopurinol as A Quorum-Sensing Inhibitor in <i>Pseudomonas aeruginosa</i> |
| title_sort | novel use of allopurinol as a quorum sensing inhibitor in i pseudomonas aeruginosa i |
| topic | quorum sensing allopurinol virulence inhibition <i>Pseudomonas aeruginosa</i> |
| url | https://www.mdpi.com/2079-6382/10/11/1385 |
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