Peptide modification results in the formation of a dimer with a 60-fold enhanced antimicrobial activity

PLoS One. 2017 Mar 15;12(3):e0173783. doi: 10.1371/journal.pone.0173783. eCollection 2017.


Cationic antimicrobial peptides (CAMPs) occur naturally in numerous organisms and are considered as a class of antibiotics with promising potential against multi-resistant bacteria. Herein, we report a strategy that can lead to the discovery of novel small CAMPs with greatly enhanced antimicrobial activity and retained antibiofilm potential. We geared our efforts towards i) the N-terminal cysteine functionalization of a previously reported small synthetic cationic peptide (peptide 1037, KRFRIRVRV-NH2), ii) its dimerization through a disulfide bond, and iii) a preliminary antimicrobial activity assessment of the newly prepared dimer against Pseudomonas aeruginosa and Burkholderia cenocepacia, pathogens responsible for the formation of biofilms in lungs of individuals with cystic fibrosis. This dimer is of high interest as it does not only show greatly enhanced bacterial growth inhibition properties compared to its pep1037 precursor (up to 60 times), but importantly, also displays antibiofilm potential at sub-MICs. Our results suggest that the reported dimer holds promise for its use in future adjunctive therapy, in combination with clinically-relevant antibiotics.

MeSH terms

  • Amino Acid Sequence
  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / pharmacology*
  • Burkholderia cenocepacia / drug effects
  • Cystic Fibrosis / microbiology
  • Dimerization
  • Humans
  • Microbial Sensitivity Tests
  • Peptides / chemistry*
  • Pseudomonas aeruginosa / drug effects


  • Anti-Infective Agents
  • Peptides

Grants and funding

JP and AC both received a Junior 1 Research Scholar Award from Fonds de recherche du Québec – Santé (29164 & 31227; JP, AC, ED and DC are supported by the Natural Sciences and Engineering Research Council of Canada ( AT is supported by an Excellence Scholarship from The Armand-Frappier Foundation of INRS University ( and a Tunisia-INRS agreement. ED holds the Canada Research Chair in Sociomicrobiology ( The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.