TY - JOUR
T1 - Bacterial membrane permeability of antimicrobial polymethacrylates
T2 - Evidence for a complex mechanism from super-resolution fluorescence imaging
AU - Michl, Thomas D.
AU - Hibbs, Ben
AU - Hyde, Lauren
AU - Postma, Almar
AU - Tran, Dung Thuy Thi
AU - Zhalgasbaikyzy, Aigerim
AU - Vasilev, Krasimir
AU - Meagher, Laurence
AU - Griesser, Hans J.
AU - Locock, Katherine E.S.
PY - 2020/5
Y1 - 2020/5
N2 - 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.
AB - 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.
KW - Antimicrobial polymer
KW - DNA binding
KW - Fluorescent tag
KW - Mechanism
KW - OMX
KW - RAFT
KW - Rhodamine RAFT agent
KW - Super-resolution imaging
UR - http://www.scopus.com/inward/record.url?scp=85082857815&partnerID=8YFLogxK
U2 - 10.1016/j.actbio.2020.03.011
DO - 10.1016/j.actbio.2020.03.011
M3 - Article
C2 - 32179195
AN - SCOPUS:85082857815
SN - 1742-7061
VL - 108
SP - 168
EP - 177
JO - Acta Biomaterialia
JF - Acta Biomaterialia
ER -