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Effect of host-mimicking medium and biofilm growth on the ability of colistin to kill Pseudomonas aeruginosa
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Sweeney, Esther, Sabnis, Akshay, Edwards, Andrew M. and Harrison, Freya (2020) Effect of host-mimicking medium and biofilm growth on the ability of colistin to kill Pseudomonas aeruginosa. Microbiology, 166 (12). pp. 1171-1180. doi:10.1099/mic.0.000995 ISSN 1350-0872.
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Official URL: http://dx.doi.org/10.1099/mic.0.000995
Abstract
In vivo biofilms cause recalcitrant infections with extensive and unpredictable antibiotic tolerance. Here, we demonstrate increased tolerance of colistin by Pseudomonas aeruginosa when grown in medium that mimics cystic fibrosis (CF) sputum versus standard medium in in vitro biofilm assays, and drastically increased tolerance when grown in an ex vivo CF model versus the in vitro assay. We used colistin conjugated to the fluorescent dye BODIPY to assess the penetration of the antibiotic into ex vivo biofilms and showed that poor penetration partly explains the high doses of drug necessary to kill bacteria in these biofilms. The ability of antibiotics to penetrate the biofilm matrix is key to their clinical success, but hard to measure. Our results demonstrate both the importance of reduced entry into the matrix in in vivo-like biofilm, and the tractability of using a fluorescent tag and benchtop fluorimeter to assess antibiotic entry into biofilms. This method could be a relatively quick, cheap and useful addition to diagnostic and drug development pipelines, allowing the assessment of drug entry into biofilms, in in vivo-like conditions, prior to more detailed tests of biofilm killing.
Item Type: | Journal Article | |||||||||
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Subjects: | Q Science > QR Microbiology R Medicine > RC Internal medicine R Medicine > RM Therapeutics. Pharmacology |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | |||||||||
Library of Congress Subject Headings (LCSH): | Antibiotics , Drug resistance in microorganisms, Biofilms, Cystic fibrosis | |||||||||
Journal or Publication Title: | Microbiology | |||||||||
Publisher: | Society for General Microbiology | |||||||||
ISSN: | 1350-0872 | |||||||||
Official Date: | 30 November 2020 | |||||||||
Dates: |
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Volume: | 166 | |||||||||
Number: | 12 | |||||||||
Page Range: | pp. 1171-1180 | |||||||||
DOI: | 10.1099/mic.0.000995 | |||||||||
Status: | Peer Reviewed | |||||||||
Publication Status: | Published | |||||||||
Access rights to Published version: | Open Access (Creative Commons) | |||||||||
Date of first compliant deposit: | 2 December 2020 | |||||||||
Date of first compliant Open Access: | 2 December 2020 | |||||||||
RIOXX Funder/Project Grant: |
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