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Evaluation of the antimicrobial activity of cationic polymers against mycobacteria : toward antitubercular macromolecules
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Phillips, Daniel J., Harrison, James, Richards, Sarah-Jane, Mitchell, Daniel E., Tichauer, Esther, Hubbard, Alasdair T. M., Guy, Collette S., Hands-Portman, Ian, Fullam, Elizabeth and Gibson, Matthew I. (2017) Evaluation of the antimicrobial activity of cationic polymers against mycobacteria : toward antitubercular macromolecules. Biomacromolecules, 18 (5). pp. 1592-1599. doi:10.1021/acs.biomac.7b00210 ISSN 1525-7797.
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Official URL: http://dx.doi.org/10.1021/acs.biomac.7b00210
Abstract
Antimicrobial resistance is a global healthcare problem with a dwindling arsenal of usable drugs. Tuberculosis, caused by Mycobacterium tuberculosis, requires long-term combination therapy and multi- and totally drug resistant strains have emerged. This study reports the antibacterial activity of cationic polymers against mycobacteria, which are distinguished from other Gram-positive bacteria by their unique cell wall comprising a covalently linked mycolic acid–arabinogalactan–peptidoglycan complex (mAGP), interspersed with additional complex lipids which helps them persist in their host. The present study finds that poly(dimethylaminoethyl methacrylate) has particularly potent antimycobacterial activity and high selectivity over two Gram-negative strains. Removal of the backbone methyl group (poly(dimethylaminoethyl acrylate)) decreased antimycobacterial activity, and poly(aminoethyl methacrylate) also had no activity against mycobacteria. Hemolysis assays revealed poly(dimethylaminoethyl methacrylate) did not disrupt red blood cell membranes. Interestingly, poly(dimethylaminoethyl methacrylate) was not found to permeabilize mycobacterial membranes, as judged by dye exclusion assays, suggesting the mode of action is not simple membrane disruption, supported by electron microscopy analysis. These results demonstrate that synthetic polycations, with the correctly tuned structure are useful tools against mycobacterial infections, for which new drugs are urgently required.
| Item Type: | Journal Article | |||||||||||||||||||||||||||||||||||||||
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| Subjects: | R Medicine > RC Internal medicine | |||||||||||||||||||||||||||||||||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Antitubercular agents, Mycobacteria, Macromolecules | |||||||||||||||||||||||||||||||||||||||
| Journal or Publication Title: | Biomacromolecules | |||||||||||||||||||||||||||||||||||||||
| Publisher: | American Chemical Society | |||||||||||||||||||||||||||||||||||||||
| ISSN: | 1525-7797 | |||||||||||||||||||||||||||||||||||||||
| Official Date: | 3 April 2017 | |||||||||||||||||||||||||||||||||||||||
| Dates: |
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| Volume: | 18 | |||||||||||||||||||||||||||||||||||||||
| Number: | 5 | |||||||||||||||||||||||||||||||||||||||
| Page Range: | pp. 1592-1599 | |||||||||||||||||||||||||||||||||||||||
| DOI: | 10.1021/acs.biomac.7b00210 | |||||||||||||||||||||||||||||||||||||||
| Status: | Peer Reviewed | |||||||||||||||||||||||||||||||||||||||
| Publication Status: | Published | |||||||||||||||||||||||||||||||||||||||
| Date of first compliant deposit: | 11 May 2017 | |||||||||||||||||||||||||||||||||||||||
| Date of first compliant Open Access: | 30 May 2017 | |||||||||||||||||||||||||||||||||||||||
| Funder: | Advantage West Midlands (AWM), European Regional Development Fund (ERDF), University of Warwick. Advanced BioImaging Research Technology Platform, Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Royal Society (Great Britain), European Research Council (ERC), Sir Henry Dale Fellowship, University of Warwick. Molecular Organisation and Assembly in Cells (MOAC), Engineering and Physical Sciences Research Council (EPSRC), University of Warwick. Institute of Advanced Study (IAS), Medical Research Council (Great Britain) (MRC) | |||||||||||||||||||||||||||||||||||||||
| Grant number: | ALERT14 award BB/M01228X/1 (BBSRC), RG120405, 104193/Z/14/Z (Royal Society (Great Britain)), CRYOMAT 638661 (ERC), EP/F500378/1, (EP/M027503/1 (EPSRC), MR/N006917/1 (MRC) | |||||||||||||||||||||||||||||||||||||||
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