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Reference: Phillips, DJ, Harrison, J, Richards, S-J et al., (2017). Evaluation of the antimicrobial activity of cationic polymers against mycobacteria: Toward antitubercular macromolecules. Biomacromolecules, 18 (5), 1592-1599.Citable link to this page:

 

Evaluation of the antimicrobial activity of cationic polymers against mycobacteria: Toward antitubercular macromolecules

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.

Publication status:PublishedPeer Review status:Peer reviewedVersion:Publisher's versionDate of acceptance:2017-03-28 Funder: University of Warwick   Funder: European Regional Development Fund   Funder: Biotechnology and Biological Sciences Research Council   Funder: Royal Society   Funder: European Research Council   Funder: Wellcome Trust   Funder: Engineering and Physical Sciences Research Council   Funder: Institute of Advanced Study   Funder: Medical Research Council   Notes:© 2017 American Chemical Society. This is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.

Bibliographic Details

Publisher: American Chemical Society

Publisher Website: http://www.acs.org/

Journal: Biomacromoleculessee more from them

Publication Website: http://pubs.acs.org/journal/bomaf6

Volume: 18

Issue: 5

Issue Date: 2017-05

pages:1592-1599Identifiers

Doi: https://doi.org/10.1021/acs.biomac.7b00210

Issn: 1526-4602

Issn: 1525-7797

Uuid: uuid:46d9c2b0-48e0-47f2-a3bd-fd3ad36900c4

Urn: uri:46d9c2b0-48e0-47f2-a3bd-fd3ad36900c4

Pubs-id: pubs:702994 Item Description

Type: journal-article;

Version: Publisher's version

Relationships





Author: Phillips, DJ - - - Harrison, J - - - Richards, S-J - - - Mitchell, DE - - - Tichauer, E - - - Hubbard, ATM - Oxford, MSD, NDM, ND

Source: https://ora.ox.ac.uk/objects/uuid:46d9c2b0-48e0-47f2-a3bd-fd3ad36900c4



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