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Lookup NU author(s): Alexander McFarlane, Dr James StachORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
To combat infection and antimicrobial resistance, it is helpful to elucidate drug mechanism(s) of action. Here we examined how the widely used antimicrobial polyhexamethylene biguanide (PHMB) kills bacteria selectively over host cells. Contrary to the accepted model of microbial membrane disruption by PHMB, we observed cell entry into a range of bacterial species, and treated bacteria displayed cell division arrest and chromosome condensation, suggesting DNA binding as an alternative antimicrobial mechanism. A DNA-level mechanism was confirmed by observations that PHMB formed nanoparticles when mixed with isolated bacterial chromosomal DNA and its effects on growth were suppressed by pairwise combination with the DNA binding ligand Hoechst 33258. PHMB also entered mammalian cells, but was trapped within endosomes and excluded from nuclei. Therefore, PHMB displays differential access to bacterial and mammalian cellular DNA and selectively binds and condenses bacterial chromosomes. Because acquired resistance to PHMB has not been reported, selective chromosome condensation provides an unanticipated paradigm for antimicrobial action that may not succumb to resistance.
Author(s): Chindera K, Mahalo M, Sharma A, Horsley H, Kloc-Muniak K, Kamaruzzamabn N, Kumar S, McFarlane A, Stach J, Bentin T, Good L
Publication type: Article
Publication status: Published
Journal: Nature Scientific Reports
Year: 2016
Volume: 6
Online publication date: 21/03/2016
Acceptance date: 29/02/2016
Date deposited: 12/04/2016
ISSN (electronic): 2045-2322
Publisher: Nature Publishing Group
URL: http://dx.doi.org/10.1038/srep23121
DOI: 10.1038/srep23121
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