Bacterial membrane permeability of antimicrobial polymethacrylates: Evidence for a complex mechanism from super-resolution fluorescence imaging

Thomas D. Michl, Ben Hibbs, Lauren Hyde, Almar Postma, Dung Thuy Thi Tran, Aigerim Zhalgasbaikyzy, Krasimir Vasilev, Laurence Meagher, Hans J. Griesser, Katherine E.S. Locock

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Amphiphilic polymers bearing cationic moieties are an emerging alternative to traditional antibiotics given their broad-spectrum activity and low susceptibility to the development of resistance. To date, however, much remains unclear regarding their mechanism of action. Using functional assays (ATP leakage, cell viability, DNA binding) and super-high resolution structured illumination microscopy (OMX-SR) of fluorescently tagged polymers, we present evidence for a complex mechanism, involving membrane permeation as well as cellular uptake, interaction with intracellular targets and possible complexation with bacterial DNA. Statement of Significance: This manuscript details the first study to systematically and directly investigate the mechanism of action of antimicrobial polymers, using super-resolution fluorescence imaging as well as functional assays. While many in the field cite membrane permeation as the sole mechanism underlying the activity of such polymers, we present evidence for multimodal actions including high cellular uptake and interaction with intracellular targets. It is also the first report to show competitive binding of antimicrobial polymers with bacterial DNA in a dose-dependent manner.

Original languageEnglish
Pages (from-to)168-177
Number of pages10
JournalActa Biomaterialia
Volume108
DOIs
Publication statusPublished - May 2020
Externally publishedYes

Keywords

  • Antimicrobial polymer
  • DNA binding
  • Fluorescent tag
  • Mechanism
  • OMX
  • RAFT
  • Rhodamine RAFT agent
  • Super-resolution imaging

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