Azithromycin Exhibits Activity Against Pseudomonas aeruginosa in Chronic Rat Lung Infection Model
Pseudomonas aeruginosa forms biofilms in the lungs of chronically infected cystic fibrosis patients, which are tolerant to both the treatment of antibiotics and the host immune system. Normally, antibiotics are less effective against bacteria growing in biofilms; azithromycin has shown a potent effi...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-04-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2021.603151/full |
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| author | Manoj Kumar Manoj Kumar Madhvi Rao Tarun Mathur Tarani Kanta Barman Vattan Joshi Tridib Chaira Smita Singhal Manisha Pandya Souhaila Al Khodor Dilip J. Upadhyay Nobuhisa Masuda |
| author_facet | Manoj Kumar Manoj Kumar Madhvi Rao Tarun Mathur Tarani Kanta Barman Vattan Joshi Tridib Chaira Smita Singhal Manisha Pandya Souhaila Al Khodor Dilip J. Upadhyay Nobuhisa Masuda |
| author_sort | Manoj Kumar |
| collection | DOAJ |
| description | Pseudomonas aeruginosa forms biofilms in the lungs of chronically infected cystic fibrosis patients, which are tolerant to both the treatment of antibiotics and the host immune system. Normally, antibiotics are less effective against bacteria growing in biofilms; azithromycin has shown a potent efficacy in cystic fibrosis patients chronically infected with P. aeruginosa and improved their lung function. The present study was conducted to evaluate the effect of azithromycin on P. aeruginosa biofilm. We show that azithromycin exhibited a potent activity against P. aeruginosa biofilm, and microscopic observation revealed that azithromycin substantially inhibited the formation of solid surface biofilms. Interestingly, we observed that azithromycin restricted P. aeruginosa biofilm formation by inhibiting the expression of pel genes, which has been previously shown to play an essential role in bacterial attachment to solid-surface biofilm. In a rat model of chronic P. aeruginosa lung infection, we show that azithromycin treatment resulted in the suppression of quorum sensing-regulated virulence factors, significantly improving the clearance of P. aeruginosa biofilms compared to that in the placebo control. We conclude that azithromycin attenuates P. aeruginosa biofilm formation, impairs its ability to produce extracellular biofilm matrix, and increases its sensitivity to the immune system, which may explain the clinical efficacy of azithromycin in cystic fibrosis patients. |
| first_indexed | 2024-12-20T04:18:32Z |
| format | Article |
| id | doaj.art-2baa9550fcb5494482ed4a5ec6e4b09b |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-20T04:18:32Z |
| publishDate | 2021-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-2baa9550fcb5494482ed4a5ec6e4b09b2022-12-21T19:53:43ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2021-04-011210.3389/fmicb.2021.603151603151Azithromycin Exhibits Activity Against Pseudomonas aeruginosa in Chronic Rat Lung Infection ModelManoj Kumar0Manoj Kumar1Madhvi Rao2Tarun Mathur3Tarani Kanta Barman4Vattan Joshi5Tridib Chaira6Smita Singhal7Manisha Pandya8Souhaila Al Khodor9Dilip J. Upadhyay10Nobuhisa Masuda11Department of Microbiology, Daiichi Sankyo India Pharma Private Limited, Gurgaon, IndiaResearch Department, Sidra Medicine, Doha, QatarDepartment of Microbiology, Daiichi Sankyo India Pharma Private Limited, Gurgaon, IndiaDepartment of Microbiology, Daiichi Sankyo India Pharma Private Limited, Gurgaon, IndiaDepartment of Microbiology, Daiichi Sankyo India Pharma Private Limited, Gurgaon, IndiaDepartment of Microbiology, Daiichi Sankyo India Pharma Private Limited, Gurgaon, IndiaDepartment of Pharmacokinetics and Metabolism, Daiichi Sankyo India Pharma Private Limited, Gurgaon, IndiaDepartment of Microbiology, Daiichi Sankyo India Pharma Private Limited, Gurgaon, IndiaDepartment of Microbiology, Daiichi Sankyo India Pharma Private Limited, Gurgaon, IndiaResearch Department, Sidra Medicine, Doha, QatarDepartment of Microbiology, Daiichi Sankyo India Pharma Private Limited, Gurgaon, IndiaDepartment of Microbiology, Daiichi Sankyo India Pharma Private Limited, Gurgaon, IndiaPseudomonas aeruginosa forms biofilms in the lungs of chronically infected cystic fibrosis patients, which are tolerant to both the treatment of antibiotics and the host immune system. Normally, antibiotics are less effective against bacteria growing in biofilms; azithromycin has shown a potent efficacy in cystic fibrosis patients chronically infected with P. aeruginosa and improved their lung function. The present study was conducted to evaluate the effect of azithromycin on P. aeruginosa biofilm. We show that azithromycin exhibited a potent activity against P. aeruginosa biofilm, and microscopic observation revealed that azithromycin substantially inhibited the formation of solid surface biofilms. Interestingly, we observed that azithromycin restricted P. aeruginosa biofilm formation by inhibiting the expression of pel genes, which has been previously shown to play an essential role in bacterial attachment to solid-surface biofilm. In a rat model of chronic P. aeruginosa lung infection, we show that azithromycin treatment resulted in the suppression of quorum sensing-regulated virulence factors, significantly improving the clearance of P. aeruginosa biofilms compared to that in the placebo control. We conclude that azithromycin attenuates P. aeruginosa biofilm formation, impairs its ability to produce extracellular biofilm matrix, and increases its sensitivity to the immune system, which may explain the clinical efficacy of azithromycin in cystic fibrosis patients.https://www.frontiersin.org/articles/10.3389/fmicb.2021.603151/fullGram-negative bacteriaPA-14PAO1multidrug resistancerespiratory tract infectionpel genes |
| spellingShingle | Manoj Kumar Manoj Kumar Madhvi Rao Tarun Mathur Tarani Kanta Barman Vattan Joshi Tridib Chaira Smita Singhal Manisha Pandya Souhaila Al Khodor Dilip J. Upadhyay Nobuhisa Masuda Azithromycin Exhibits Activity Against Pseudomonas aeruginosa in Chronic Rat Lung Infection Model Frontiers in Microbiology Gram-negative bacteria PA-14 PAO1 multidrug resistance respiratory tract infection pel genes |
| title | Azithromycin Exhibits Activity Against Pseudomonas aeruginosa in Chronic Rat Lung Infection Model |
| title_full | Azithromycin Exhibits Activity Against Pseudomonas aeruginosa in Chronic Rat Lung Infection Model |
| title_fullStr | Azithromycin Exhibits Activity Against Pseudomonas aeruginosa in Chronic Rat Lung Infection Model |
| title_full_unstemmed | Azithromycin Exhibits Activity Against Pseudomonas aeruginosa in Chronic Rat Lung Infection Model |
| title_short | Azithromycin Exhibits Activity Against Pseudomonas aeruginosa in Chronic Rat Lung Infection Model |
| title_sort | azithromycin exhibits activity against pseudomonas aeruginosa in chronic rat lung infection model |
| topic | Gram-negative bacteria PA-14 PAO1 multidrug resistance respiratory tract infection pel genes |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2021.603151/full |
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