Real-Time Observation of Antimicrobial Polycation Effects on Escherichia coli : Adapting the Carpet Model for Membrane Disruption to Quaternary Copolyoxetanes

Real-time atomic force microscopy (AFM) was used for analyzing effects of the antimicrobial polycation copolyoxetane P[(C12)-(ME2Ox)-50/50], C12-50 on the membrane of a model bacterium, Escherichia coli (ATCC# 35218). AFM imaging showed cell membrane changes with increasing C12-50 concentration and...

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Veröffentlicht in:Langmuir : the ACS journal of surfaces and colloids. - 1985. - 32(2016), 12 vom: 29. März, Seite 2975-84
1. Verfasser: Wang, Congzhou (VerfasserIn)
Weitere Verfasser: Zolotarskaya, Olga Y, Nair, Sithara S, Ehrhardt, Christopher J, Ohman, Dennis E, Wynne, Kenneth J, Yadavalli, Vamsi K
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2016
Zugriff auf das übergeordnete Werk:Langmuir : the ACS journal of surfaces and colloids
Schlagworte:Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Anti-Bacterial Agents Polyurethanes Surface-Active Agents copolyoxetane C12-50 Polylysine 25104-18-1
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520 |a Real-time atomic force microscopy (AFM) was used for analyzing effects of the antimicrobial polycation copolyoxetane P[(C12)-(ME2Ox)-50/50], C12-50 on the membrane of a model bacterium, Escherichia coli (ATCC# 35218). AFM imaging showed cell membrane changes with increasing C12-50 concentration and time including nanopore formation and bulges associated with outer bacterial membrane disruption. A macroscale bactericidal concentration study for C12-50 showed a 4 log kill at 15 μg/mL with conditions paralleling imaging (1 h, 1x PBS, physiological pH, 25 °C). The dramatic changes from the control image to 1 h after introducing 15 μg/mL C12-50 are therefore reasonably attributed to cell death. At the highest concentration (60 μg/mL) further cell membrane disruption results in leakage of cytoplasm driven by detergent-like action. The sequence of processes for initial membrane disruption by the synthetic polycation C12-50 follows the carpet model posited for antimicrobial peptides (AMPs). However, the nanoscale details are distinctly different as C12-50 is a synthetic, water-soluble copolycation that is best modeled as a random coil. In a complementary AFM study, chemical force microscopy shows that incubating cells with C12-50 decreased the hydrophobicity across the entire cell surface at an early stage. This finding provides additional evidence indicating that C12-50 polycations initially bind with the cell membrane in a carpet-like fashion. Taken together, real time AFM imaging elucidates the mechanism of antimicrobial action for copolyoxetane C12-50 at the single cell level. In future work this approach will provide important insights into structure-property relationships and improved antimicrobial effectiveness for synthetic amphiphilic polycations 
650 4 |a Journal Article 
650 4 |a Research Support, N.I.H., Extramural 
650 4 |a Research Support, Non-U.S. Gov't 
650 4 |a Research Support, U.S. Gov't, Non-P.H.S. 
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650 7 |a Polyurethanes  |2 NLM 
650 7 |a Surface-Active Agents  |2 NLM 
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650 7 |a Polylysine  |2 NLM 
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700 1 |a Zolotarskaya, Olga Y  |e verfasserin  |4 aut 
700 1 |a Nair, Sithara S  |e verfasserin  |4 aut 
700 1 |a Ehrhardt, Christopher J  |e verfasserin  |4 aut 
700 1 |a Ohman, Dennis E  |e verfasserin  |4 aut 
700 1 |a Wynne, Kenneth J  |e verfasserin  |4 aut 
700 1 |a Yadavalli, Vamsi K  |e verfasserin  |4 aut 
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