Maculatin 1.1 disrupts staphylococcus aureus lipid membranes via a pore mechanism
Date
2013
Authors
Sani, M.
Whitwell, T.
Gehman, J.
Robins-Browne, R.
Pantarat, N.
Attard, T.
Reynolds, E.
O'Brien-Simpson, N.
Separovic, F.
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Journal article
Citation
Antimicrobial Agents and Chemotherapy, 2013; 57(8):3593-3600
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
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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.
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© 2013, American Society for Microbiology. All Rights Reserved.