Biophysical investigation into the antibacterial action of modelin-5-NH2

Journal article


Dennison, S, Hauß, T, Badiani, K, Harris, F and Phoenix, D (2019). Biophysical investigation into the antibacterial action of modelin-5-NH2. Soft Matter.
AuthorsDennison, S, Hauß, T, Badiani, K, Harris, F and Phoenix, D
Abstract

Modelin-5-CONH2 (M5-NH2) is a synthetic antimicrobial peptide, which was found to show potent activity against Bacillus subtilis (Minimum lethal concentration = 8.47 μM) and to bind strongly to membranes of the organism (Kd = 10.44 μM). The peptide adopted high levels of amphiphilic α-helical structure in the presence of these membranes (> 50 %), which led to high levels of insertion (Δπ ≥ 8.0 mN m-1). M5-NH2 showed high affinity for anionic lipid (Kd = 7.46 µM) and zwitterionic lipid (Kd = 14.7 µM), which drove insertion into membranes formed from these lipids (Δπ = 11.5 and 3.5 mN m-1, respectively) and interactions with their head group and hydrophobic core regions. Neutron diffraction studies showed that M5-NH2 inserted into B. subtilis membranes with its N-terminal residue, L16, located 5.5 Å from the membrane centre, in the acyl chain region of these membranes, and promoted a reduction in membrane thickness of circa 1.8 Å or 5 % of membrane width. Insertion into B. subtilis membranes by the peptide also promoted other effects associated with membrane thinning, including increases in membrane surface area (Cs-1 decrease) and fluidity (ΔGmix > 0 to < 0). Membrane insertion and thinning by M5-NH2 induced high levels of lysis (> 55 %) and, taken with MD simulation data, it is speculated that the antibacterial action of the peptide may involve the toroidal pore, carpet or tilted-type mechanism of membrane permeabilization.

Year2019
JournalSoft Matter
PublisherRoyal Society of Chemistry
ISSN1744-683X
Digital Object Identifier (DOI)doi:10.1039/C8SM02374C
Publication dates
Print30 Apr 2019
Publication process dates
Deposited11 May 2019
Accepted30 Apr 2019
Accepted author manuscript
License
CC BY 4.0
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https://openresearch.lsbu.ac.uk/item/866vz

Accepted author manuscript

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