EcDBS1R6: A novel cationic antimicrobial peptide derived from a signal peptide sequence

William F. Porto, Luz N. Irazazabal, Vincent Humblot, Evan F. Haney, Suzana M. Ribeiro, Robert E.W. Hancock, Ali Ladram, Octavio L. Franco

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Background: Bacterial infections represent a major worldwide health problem the antimicrobial peptides (AMPs) have been considered as potential alternative agents for treating these infections. Here we demonstrated the antimicrobial activity of EcDBS1R6, a peptide derived from a signal peptide sequence of Escherichia coli that we previously turned into an AMP by making changes through the Joker algorithm. Methods: Antimicrobial activity was measured by broth microdilution method. Membrane integrity was measured using fluorescent probes and through scanning electron microscopy imaging. A sliding window of truncated peptides was used to determine the EcDBS1R6 active core. Molecular dynamics in TFE/water environment was used to assess the EcDBS1R6 structure. Results: Signal peptides are known to naturally interact with membranes; however, the modifications introduced by Joker transformed this peptide into a membrane-active agent capable of killing bacteria. The C-terminus was unable to fold into an α-helix whereas its fragments showed poor or no antimicrobial activity, suggesting that the EcDBS1R6 antibacterial core was located at the helical N-terminus, corresponding to the signal peptide portion of the parent peptide. Conclusion: The strategy of transforming signal peptides into AMPs appears to be promising and could be used to produce novel antimicrobial agents. General significance: The process of transforming an inactive signal peptide into an antimicrobial peptide could open a new venue for creating new AMPs derived from signal peptides.

Original languageEnglish
Article number129633
JournalBiochimica et Biophysica Acta - General Subjects
Volume1864
Issue number9
DOIs
Publication statusPublished or Issued - Sep 2020
Externally publishedYes

Keywords

  • Joker algorithm
  • Mechanism of action
  • Membrane damage
  • Rational design
  • Sliding window

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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