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|dc.identifier.citation||Antimicrobial Agents and Chemotherapy, 2013; 57(8):3593-3600||en|
|dc.description.abstract||Maculatin 1.1 (Mac1) showed potent activity against Staphylococcus aureus with an MIC of 7 μM. The mode of action of Mac1 was investigated by combining assays with S. aureus cells and lipid vesicles mimicking their membrane composition. A change in Mac1 conformation was monitored by circular dichroism from random coil to ca. 70% α-helix structure in contact with vesicles. Electron micrographs of S. aureus incubated with Mac1 showed rough and rippled cell surfaces. An uptake of 65% of small (FD, 4 kDa [FD-4]) and 35% of large (RD, 40 kDa [RD-40]) fluorescent dextrans by S. aureus was observed by flow cytometry and indicate that Mac1 formed a pore of finite size. In model membranes with both dyes encapsulated together, the full release of FD-4 occurred, but only 40% of RD-40 was reached, supporting the flow cytometry results, and indicating a pore size between 1.4 and 4.5 nm. Finally, solid-state nuclear magnetic resonance showed formation of an isotropic phase signifying highly mobile lipids such as encountered in a toroidal pore structure. Overall, Mac1 is a promising antimicrobial peptide with the potent capacity to form pores in S. aureus membranes.||en|
|dc.description.statementofresponsibility||M.-A. Sani, T. C. Whitwell, J. D. Gehman, R. M. Robins-Browne, N. Pantarat, T. J. Attard, E. C. Reynolds, N. M. O'Brien-Simpson and F. Separovic||en|
|dc.publisher||American Society for Microbiology||en|
|dc.rights||© 2013, American Society for Microbiology. All Rights Reserved.||en|
|dc.subject||Cell Membrane; Staphylococcus aureus; Dextrans; Lipid Bilayers; Antimicrobial Cationic Peptides; Amphibian Proteins; Anti-Bacterial Agents; Microscopy, Electron, Scanning; Circular Dichroism; Drug Evaluation, Preclinical; Cell Membrane Permeability; Protein Structure, Secondary; Molecular Weight; Fluorescence; Porosity||en|
|dc.title||Maculatin 1.1 disrupts staphylococcus aureus lipid membranes via a pore mechanism||en|
|Appears in Collections:||Medicine publications|
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