Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/99148
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Type: Journal article
Title: Maculatin 1.1 disrupts staphylococcus aureus lipid membranes via a pore mechanism
Author: Sani, M.
Whitwell, T.
Gehman, J.
Robins-Browne, R.
Pantarat, N.
Attard, T.
Reynolds, E.
O'Brien-Simpson, N.
Separovic, F.
Citation: Antimicrobial Agents and Chemotherapy, 2013; 57(8):3593-3600
Publisher: American Society for Microbiology
Issue Date: 2013
ISSN: 0066-4804
1098-6596
Statement of
Responsibility: 
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
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.
Keywords: 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
Rights: © 2013, American Society for Microbiology. All Rights Reserved.
RMID: 0030048059
DOI: 10.1128/AAC.00195-13
Grant ID: http://purl.org/au-research/grants/arc/DP110101866
http://purl.org/au-research/grants/nhmrc/1008106
Appears in Collections:Medicine publications

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