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

David Phoenix

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

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 ) 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.
Original languageEnglish
JournalMolecular and Cellular Biochemistry
DOIs
Publication statusPublished - 6 Jun 2021

Keywords

  • α-Helical structure
  • pH dependent with alkaline optimum
  • Linearized esculentin 2EM (E2EM-lin)
  • Preference for gram-positive bacteria
  • Tilted peptide

Fingerprint

Dive into the research topics of 'Linearized esculentin-2EM shows pH dependent antibacterial activity with an alkaline optimum.'. Together they form a unique fingerprint.

Cite this