Amino Acids

, Volume 48, Issue 2, pp 505–522 | Cite as

Design and membrane-disruption mechanism of charge-enriched AMPs exhibiting cell selectivity, high-salt resistance, and anti-biofilm properties

Original Article

Abstract

Cationic antimicrobial peptides (AMPs) are essential components of the innate immune system, offering protection against invading pathogenic bacteria. In nature, AMPs serve as antibiotics with broad-spectrum antimicrobial and anti-biofilm properties. However, low effective stability in high-salt environments and physiological instability in biological membranes limit the applicability of naturally occurring AMPs as novel therapeutics. We therefore designed short synthetic cationic peptides by substituting key residues in myxinidin, an AMP derived from the epidermal mucus of hagfish, with lysine (Lys, K), arginine (Arg, R), and tryptophan (Trp, W). The resultant myxinidin analogs exhibited strong antimicrobial activity against both Gram-positive and Gram-negative bacteria, including multidrug-resistant strains, even under high-salt conditions. Moreover, these peptides showed high binding affinity for both lipopolysaccharides and lipoteichoic acids and inhibited biofilm formation by most bacteria, but did not cause significant lysis of human red blood cells and were not cytotoxic to normal human keratinocytes. Circular dichroism analysis revealed that myxinidin and its analogs assumed α-helical or β-sheet structures within artificial liposomes and bacterial membranes. In addition, bacterial killing and membrane permeation experiments demonstrated that the myxinidin analogs permeated through bacterial membranes, leading to cytoplasmic disruption and cell death. Taken together, these findings suggest myxinidin analogs may be promising candidate antibiotic agents for therapeutic application against antibiotic-resistant bacteria.

Keywords

Antimicrobial peptide Anti-biofilm Circular dichroism Antibiotic-resistant bacteria 

Supplementary material

726_2015_2104_MOESM1_ESM.docx (185 kb)
Supplementary material 1 (DOCX 184 kb)

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Copyright information

© Springer-Verlag Wien 2015

Authors and Affiliations

  • Hyo Mi Han
    • 1
  • Ramamourthy Gopal
    • 1
  • Yoonkyung Park
    • 1
    • 2
  1. 1.Department of Biomedical ScienceChosun UniversityGwangjuKorea
  2. 2.Research Center for Proteineous MaterialsChosun UniversityGwangjuKorea

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