Mannitol enhances antibiotic sensitivity of persister bacteria in Pseudomonas aeruginosa biofilms
The failure of antibiotic therapies to clear Pseudomonas aeruginosa lung infection, the key mortality factor for cystic fibrosis (CF) patients, is partly attributed to the high tolerance of P. aeruginosa biofilms. Mannitol has previously been found to restore aminoglycoside sensitivity in Escherichi...
| Main Authors: | , , , |
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| Format: | Journal Article |
| Language: | English |
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2014
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| Online Access: | https://hdl.handle.net/10356/80009 http://hdl.handle.net/10220/18797 |
| _version_ | 1824455725751992320 |
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| author | Rice, Scott A. Barraud, Nicolas Buson, Alberto Jarolimek, Wolfgang |
| author2 | Beloin, Christophe |
| author_facet | Beloin, Christophe Rice, Scott A. Barraud, Nicolas Buson, Alberto Jarolimek, Wolfgang |
| author_sort | Rice, Scott A. |
| collection | NTU |
| description | The failure of antibiotic therapies to clear Pseudomonas aeruginosa lung infection, the key mortality factor for cystic fibrosis (CF) patients, is partly attributed to the high tolerance of P. aeruginosa biofilms. Mannitol has previously been found to restore aminoglycoside sensitivity in Escherichia coli by generating a proton-motive force (PMF), suggesting a potential new strategy to improve antibiotic therapy and reduce disease progression in CF. Here, we used the commonly prescribed aminoglycoside tobramycin to select for P. aeruginosa persister cells during biofilm growth. Incubation with mannitol (10–40 mM) increased tobramycin sensitivity of persister cells up to 1,000-fold. Addition of mannitol to pre-grown biofilms was able to revert the persister phenotype and improve the efficacy of tobramycin. This effect was blocked by the addition of a PMF inhibitor or in a P. aeruginosa mutant strain unable to metabolise mannitol. Addition of glucose and NaCl at high osmolarity also improved the efficacy of tobramycin although to a lesser extent compared to mannitol. Therefore, the primary effect of mannitol in reverting biofilm associated persister cells appears to be an active, physiological response, associated with a minor contribution of osmotic stress. Mannitol was tested against clinically relevant strains, showing that biofilms containing a subpopulation of persister cells are better killed in the presence of mannitol, but a clinical strain with a high resistance to tobramycin was not affected by mannitol. Overall, these results suggest that in addition to improvements in lung function by facilitating mucus clearance in CF, mannitol also affects antibiotic sensitivity in biofilms and does so through an active, physiological response. |
| first_indexed | 2025-02-19T03:42:47Z |
| format | Journal Article |
| id | ntu-10356/80009 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2025-02-19T03:42:47Z |
| publishDate | 2014 |
| record_format | dspace |
| spelling | ntu-10356/800092022-02-16T16:30:58Z Mannitol enhances antibiotic sensitivity of persister bacteria in Pseudomonas aeruginosa biofilms Rice, Scott A. Barraud, Nicolas Buson, Alberto Jarolimek, Wolfgang Beloin, Christophe School of Biological Sciences Singapore Centre for Environmental Life Sciences Engineering DRNTU::Science::Biological sciences::Microbiology::Bacteria The failure of antibiotic therapies to clear Pseudomonas aeruginosa lung infection, the key mortality factor for cystic fibrosis (CF) patients, is partly attributed to the high tolerance of P. aeruginosa biofilms. Mannitol has previously been found to restore aminoglycoside sensitivity in Escherichia coli by generating a proton-motive force (PMF), suggesting a potential new strategy to improve antibiotic therapy and reduce disease progression in CF. Here, we used the commonly prescribed aminoglycoside tobramycin to select for P. aeruginosa persister cells during biofilm growth. Incubation with mannitol (10–40 mM) increased tobramycin sensitivity of persister cells up to 1,000-fold. Addition of mannitol to pre-grown biofilms was able to revert the persister phenotype and improve the efficacy of tobramycin. This effect was blocked by the addition of a PMF inhibitor or in a P. aeruginosa mutant strain unable to metabolise mannitol. Addition of glucose and NaCl at high osmolarity also improved the efficacy of tobramycin although to a lesser extent compared to mannitol. Therefore, the primary effect of mannitol in reverting biofilm associated persister cells appears to be an active, physiological response, associated with a minor contribution of osmotic stress. Mannitol was tested against clinically relevant strains, showing that biofilms containing a subpopulation of persister cells are better killed in the presence of mannitol, but a clinical strain with a high resistance to tobramycin was not affected by mannitol. Overall, these results suggest that in addition to improvements in lung function by facilitating mucus clearance in CF, mannitol also affects antibiotic sensitivity in biofilms and does so through an active, physiological response. Published version 2014-02-14T06:57:53Z 2019-12-06T13:38:40Z 2014-02-14T06:57:53Z 2019-12-06T13:38:40Z 2013 2013 Journal Article Barraud, N., Buson, A., Jarolimek, W., & Rice, S. A. (2013). Mannitol Enhances Antibiotic Sensitivity of Persister Bacteria in Pseudomonas aeruginosa Biofilms. PLoS ONE, 8(12), e84220. 1932-6203 https://hdl.handle.net/10356/80009 http://hdl.handle.net/10220/18797 10.1371/journal.pone.0084220 24349568 en PLoS ONE © 2013 Barraud et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. application/pdf |
| spellingShingle | DRNTU::Science::Biological sciences::Microbiology::Bacteria Rice, Scott A. Barraud, Nicolas Buson, Alberto Jarolimek, Wolfgang Mannitol enhances antibiotic sensitivity of persister bacteria in Pseudomonas aeruginosa biofilms |
| title | Mannitol enhances antibiotic sensitivity of persister bacteria in Pseudomonas aeruginosa biofilms |
| title_full | Mannitol enhances antibiotic sensitivity of persister bacteria in Pseudomonas aeruginosa biofilms |
| title_fullStr | Mannitol enhances antibiotic sensitivity of persister bacteria in Pseudomonas aeruginosa biofilms |
| title_full_unstemmed | Mannitol enhances antibiotic sensitivity of persister bacteria in Pseudomonas aeruginosa biofilms |
| title_short | Mannitol enhances antibiotic sensitivity of persister bacteria in Pseudomonas aeruginosa biofilms |
| title_sort | mannitol enhances antibiotic sensitivity of persister bacteria in pseudomonas aeruginosa biofilms |
| topic | DRNTU::Science::Biological sciences::Microbiology::Bacteria |
| url | https://hdl.handle.net/10356/80009 http://hdl.handle.net/10220/18797 |
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