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 |
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Erscheinungsjahr: |
2021 |
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Erschienen: |
2021 |
Enthalten in: |
Zur Gesamtaufnahme - volume:476 |
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Enthalten in: |
Molecular and cellular biochemistry - 476(2021), 10 vom: 06. Okt., Seite 3729-3744 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Malik, Erum [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Completed 01.09.2021 Date Revised 28.02.2022 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1007/s11010-021-04181-7 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM326400397 |
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520 | |a © 2021. The Author(s). | ||
520 | |a 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 | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Linearized esculentin 2EM (E2EM-lin) | |
650 | 4 | |a Preference for gram-positive bacteria | |
650 | 4 | |a Tilted peptide | |
650 | 4 | |a pH dependent with alkaline optimum | |
650 | 4 | |a α-Helical structure | |
650 | 7 | |a Amphibian Proteins |2 NLM | |
650 | 7 | |a Anti-Bacterial Agents |2 NLM | |
650 | 7 | |a Antimicrobial Cationic Peptides |2 NLM | |
650 | 7 | |a esculentin protein, Rana esculenta |2 NLM | |
700 | 1 | |a Phoenix, David A |e verfasserin |4 aut | |
700 | 1 | |a Snape, Timothy J |e verfasserin |4 aut | |
700 | 1 | |a Harris, Frederick |e verfasserin |4 aut | |
700 | 1 | |a Singh, Jaipaul |e verfasserin |4 aut | |
700 | 1 | |a Morton, Leslie H G |e verfasserin |4 aut | |
700 | 1 | |a Dennison, Sarah R |e verfasserin |4 aut | |
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