Maculatin 1.1 Disrupts Staphylococcus aureus Lipid Membranes via a Pore Mechanism

作者：Sani M A^*; Whitwell T C; Gehman J D; Robins Browne R M; Pantarat N; Attard T J; Reynolds E C; O'Brien Simpson N M; Separovic F

来源：Antimicrobial Agents and Chemotherapy, 2013, 57(8): 3593-3600.

DOI：10.1128/AAC.00195-13

Maculatin 1.1 (Mac1) showed potent activity against Staphylococcus aureus with an MIC of 7 mu M. 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% alpha-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.

• 出版日期2013-8