Efficacy of designer K11 antimicrobial peptide (a hybrid of melittin, cecropin A1 and magainin 2) against Acinetobacter baumannii-infected wounds

Pathog Dis. 2018 Oct 1;76(7). doi: 10.1093/femspd/fty072.

Abstract

Due to emergence of multidrug resistance in pathogens, the attention of the scientific community is now directed towards strengthening the reservoir of antimicrobial compounds. Prior to in vivo studies, the interaction and penetration of a hybrid peptide K11 in bacterial cells using confocal microscopy was assessed which was observed as early as 10 min after incubation with the peptide. Cell lysis along with leakage of cytoplasmic content was confirmed by electron microscopy. To evaluate the in vivo performance of the peptide, it was contained in carbopol hydrogel. Efficacy of the hydrogel formulation was then evaluated against Acinetobacter baumannii-infected wounds using a murine excision model. Treatment resulted in restoration of body weight, complete clearance of infection from the wound by day 7 and 99% wound enclosure by day 21, in contrast to the persistence of infection and 70% wound enclosure in the infected group. Further, this treatment resulted in a 2.6-fold decrease in the levels of malondialdehyde along with a 4.5-fold increase in the levels of catalase on day 3. Appearance of normal histo-architecture was observed in the treatment group. Based on these results, the peptide hydrogel can be exploited in future as one of the strategies for developing a topical anti-infective therapeutic agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter Infections / drug therapy*
  • Acinetobacter Infections / microbiology
  • Acinetobacter baumannii / drug effects
  • Acinetobacter baumannii / ultrastructure
  • Animals
  • Anti-Infective Agents / administration & dosage*
  • Anti-Infective Agents / pharmacology
  • Antimicrobial Cationic Peptides / administration & dosage*
  • Antimicrobial Cationic Peptides / genetics
  • Antimicrobial Cationic Peptides / pharmacology
  • Disease Models, Animal
  • Hydrogel, Polyethylene Glycol Dimethacrylate / administration & dosage
  • Magainins / administration & dosage*
  • Magainins / genetics
  • Magainins / pharmacology
  • Melitten / administration & dosage*
  • Melitten / genetics
  • Melitten / pharmacology
  • Mice
  • Microscopy, Confocal
  • Microscopy, Electron
  • Recombinant Fusion Proteins / administration & dosage*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / pharmacology
  • Time Factors
  • Treatment Outcome
  • Wound Healing
  • Wound Infection / drug therapy*
  • Wound Infection / microbiology
  • Xenopus Proteins / administration & dosage*
  • Xenopus Proteins / genetics
  • Xenopus Proteins / pharmacology

Substances

  • Anti-Infective Agents
  • Antimicrobial Cationic Peptides
  • Magainins
  • Recombinant Fusion Proteins
  • Xenopus Proteins
  • magainin 2 peptide, Xenopus
  • Melitten
  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • cecropin A