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Persistent URL http://purl.org/net/epubs/work/48071081
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Record Id 48071081
Title How do Self-Assembling Antimicrobial Lipopeptides Kill Bacteria?
Contributors
Abstract Antimicrobial peptides are promising alternatives to traditional antibiotics. A group of self-assembling lipopeptides was formed by attaching an acyl chain to the N-terminus of α-helixforming peptides with the sequence Cx-G(IIKK)yI-NH2 (CxGy, x = 4−12 and y = 2). CxGy self-assemble into nanofibers above their critical aggregation concentrations (CACs). With increasing x, the CACs decrease and the hydrophobic interactions increase, promoting secondary structure transitions within the nanofibers. Antimicrobial activity, determined by the minimum inhibition concentration (MIC), also decreases with increasing x, but the MICs are significantly smaller than the CACs, suggesting effective bacterial membrane-disrupting power. Unlike conventional antibiotics, both C8G2 and C12G2 can kill Staphylococcus aureus and Escherichia coli after only minutes of exposure under the concentrations studied. C12G2 nanofibers have considerably faster killing dynamics and lower cytotoxicity than their nonaggregated monomers. Antimicrobial activity of peptide aggregates has, to date, been underexploited, and it is found to be a very promising mechanism for peptide design. Detailed evidence for the molecular mechanisms involved is provided, based on super-resolution fluorescence microscopy, solid-state nuclear magnetic resonance, atomic force microscopy, neutron scattering/reflectivity, circular dichroism, and Brewster angle microscopy.
Organisation ISIS , ISIS-LOQ , ISIS-SURF , STFC
Keywords
Funding Information AstraZeneca; University of Manchester; STFC; CSC; BBSRC (BB/S018492/1); Syngenta
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Language English (EN)
Type Details URI(s) Local file(s) Year
Journal Article ACS Appl Mater Inter 12, no. 50 (2020): 55675-55687. doi:10.1021/acsami.0c17222 2020