Linearized esculentin-2EM shows pH dependent antibacterial activity with an alkaline optimum

© 2021. The Author(s)..

Here the hypothesis that linearized esculentin 2EM (E2EM-lin) from Glandirana emeljanovi possesses pH dependent activity is investigated. The peptide showed weak activity against Gram-negative bacteria (MLCs ≥ 75.0 μM) but potent efficacy towards Gram-positive bacteria (MLCs ≤ 6.25 μM). E2EM-lin adopted an α-helical structure in the presence of bacterial membranes that increased as pH was increased from 6 to 8 (↑ 15.5-26.9%), whilst similar increases in pH enhanced the ability of the peptide to penetrate (↑ 2.3-5.1 mN m-1) and lyse (↑ 15.1-32.5%) these membranes. Theoretical analysis predicted that this membranolytic mechanism involved a tilted segment, that increased along the α-helical long axis of E2EM-lin (1-23) in the N → C direction, with -  < µH > increasing overall from circa - 0.8 to - 0.3. In combination, these data showed that E2EM-lin killed bacteria via novel mechanisms that were enhanced by alkaline conditions and involved the formation of tilted and membranolytic, α-helical structure. The preference of E2EM-lin for Gram-positive bacteria over Gram-negative organisms was primarily driven by the superior ability of phosphatidylglycerol to induce α-helical structure in the peptide as compared to phosphatidylethanolamine. These data were used to generate a novel pore-forming model for the membranolytic activity of E2EM-lin, which would appear to be the first, major reported instance of pH dependent AMPs with alkaline optima using tilted structure to drive a pore-forming process. It is proposed that E2EM-lin has the potential for development to serve purposes ranging from therapeutic usage, such as chronic wound disinfection, to food preservation by killing food spoilage organisms.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:476

Enthalten in:

Molecular and cellular biochemistry - 476(2021), 10 vom: 06. Okt., Seite 3729-3744

Sprache:

Englisch

Beteiligte Personen:

Malik, Erum [VerfasserIn]
Phoenix, David A [VerfasserIn]
Snape, Timothy J [VerfasserIn]
Harris, Frederick [VerfasserIn]
Singh, Jaipaul [VerfasserIn]
Morton, Leslie H G [VerfasserIn]
Dennison, Sarah R [VerfasserIn]

Links:

Volltext

Themen:

α-Helical structure
Amphibian Proteins
Anti-Bacterial Agents
Antimicrobial Cationic Peptides
Esculentin protein, Rana esculenta
Journal Article
Linearized esculentin 2EM (E2EM-lin)
PH dependent with alkaline optimum
Preference for gram-positive bacteria
Tilted peptide

Anmerkungen:

Date Completed 01.09.2021

Date Revised 28.02.2022

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1007/s11010-021-04181-7

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM326400397