Bacterial susceptibility and resistance to modelin-5.

Journal article

Dennison, S., Morton, L. H., Badiani, K., Harris, F. and Phoenix, D. (2023). Bacterial susceptibility and resistance to modelin-5. Soft Matter. 19 (42), pp. 8247-8263. https://doi.org/10.1039/d3sm01007d
AuthorsDennison, S., Morton, L. H., Badiani, K., Harris, F. and Phoenix, D.
AbstractModelin-5 (M5-NH ) killed with a minimum lethal concentration (MLC) of 5.86 μM and strongly bound its cytoplasmic membrane (CM) with a of 23.5 μM. The peptide adopted high levels of amphiphilic α-helical structure (75.0%) and penetrated the CM hydrophobic core (8.0 mN m ). This insertion destabilised CM structure increased lipid packing and decreased fluidity (Δ < 0), which promoted high levels of lysis (84.1%) and cell death. M5-NH showed a very strong affinity ( = 3.5 μM) and very high levels of amphiphilic α-helical structure with cardiolipin membranes (96.0%,) which primarily drove the peptide's membranolytic action against . In contrast, M5-NH killed with an MLC of 147.6 μM and weakly bound its CM with a of 117.6 μM, The peptide adopted low levels of amphiphilic α-helical structure (35.0%) and only penetrated the upper regions of the CM (3.3 mN m ). This insertion stabilised CM structure decreased lipid packing and increased fluidity (Δ > 0) and promoted only low levels of lysis (24.3%). The insertion and lysis of the CM by M5-NH showed a strong negative correlation with its lysyl phosphatidylglycerol (Lys-PG) content ( > 0.98). In combination, these data suggested that Lys-PG mediated mechanisms inhibited the membranolytic action of M5-NH against , thereby rendering the organism resistant to the peptide. These results are discussed in relation to structure/function relationships of M5-NH and CM lipids that underpin bacterial susceptibility and resistance to the peptide.
KeywordsAntimicrobial Cationic Peptides - chemistry; Staphylococcus aureus; Anti-Bacterial Agents - chemistry; Cell Membrane - chemistry; Membrane Lipids - chemistry
Year2023
JournalSoft Matter
Journal citation19 (42), pp. 8247-8263
PublisherRoyal Society of Chemistry (RSC)
ISSN1744-6848
Digital Object Identifier (DOI)https://doi.org/10.1039/d3sm01007d
Publication dates
Online01 Nov 2023
Publication process dates
Deposited21 Nov 2023
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Open
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