Transdermally administered proline-arginine-rich host defense peptides show systemic efficacy in a lethal mouse bacteremia model

Amino Acids. 2017 Sep;49(9):1647-1651. doi: 10.1007/s00726-017-2457-7. Epub 2017 Jun 29.

Abstract

Host defense peptides are preferably administered as topical therapeutic agents. We have investigated whether peptide A3-APO can enter the circulation when applied to the ear skin. Efficacy of peptide monotherapy as transdermal administration option was assessed in a systemic mouse Acinetobacter baumannii model. A3-APO reduced mortality and demonstrated a statistically significant reduction of blood bacterial counts, regardless whether it was administered prior or after bacterial challenge. The peptidic metabolite of A3-APO was efficacious when applied to the ear or tail.

Keywords: Bacterial counts; Multidrug resistance; Peptide antibiotic; Skin penetration; Survival.

MeSH terms

  • Acinetobacter Infections / drug therapy*
  • Acinetobacter Infections / microbiology
  • Acinetobacter Infections / mortality
  • Acinetobacter Infections / pathology
  • Acinetobacter baumannii / drug effects*
  • Acinetobacter baumannii / pathogenicity
  • Acinetobacter baumannii / physiology
  • Administration, Cutaneous
  • Amino Acid Sequence
  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Antimicrobial Cationic Peptides / pharmacology*
  • Arginine / chemistry
  • Bacteremia / drug therapy*
  • Bacteremia / microbiology
  • Bacteremia / mortality
  • Bacteremia / pathology
  • Bacterial Load / drug effects
  • Carbapenems / pharmacology
  • Colistin / pharmacology
  • Disease Models, Animal
  • Drug Resistance, Multiple, Bacterial / drug effects*
  • Ear
  • Humans
  • Mice
  • Proline / chemistry
  • Skin / metabolism
  • Survival Analysis

Substances

  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • Carbapenems
  • Arginine
  • Proline
  • Colistin