Linearized esculentin-2EM shows pH dependent antibacterial activity with an alkaline optimum
| Autor: | David A. Phoenix, Jaipaul Singh, L.H.G. Morton, Timothy J. Snape, Erum Malik, Sarah R. Dennison, Frederick Harris |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Protein Conformation alpha-Helical Tilted peptide Lysis Clinical Biochemistry Food spoilage Peptide Gram-Positive Bacteria Article Amphibian Proteins 030207 dermatology & venereal diseases 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine α-Helical structure Linearized esculentin 2EM (E2EM-lin) pH dependent with alkaline optimum Molecular Biology Phosphatidylethanolamine Phosphatidylglycerol chemistry.chemical_classification biology Cell Biology General Medicine Preference for gram-positive bacteria Hydrogen-Ion Concentration biology.organism_classification C700 Anti-Bacterial Agents 030104 developmental biology Membrane chemistry Biophysics Antibacterial activity Bacteria Antimicrobial Cationic Peptides |
| Zdroj: | Molecular and Cellular Biochemistry |
| ISSN: | 1573-4919 0300-8177 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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