Use of tilapia piscidin 3 (TP3) to protect against MRSA infection in mice with skin injuries

Oncotarget. 2015 May 30;6(15):12955-69. doi: 10.18632/oncotarget.4102.

Abstract

Antimicrobial peptides (AMPs), represent promising agents for new therapeutic approaches of infected wound treatment, on account of their antimicrobial and wound closure activities, and low potential for inducing resistance. However, therapeutic applications of these AMPs are limited by their toxicity and low stability in vivo. Previously, we reported that the 23 amino-acid designer peptide TP3 possessed antimicrobial activities. Here, we analyzed the wound closure activities of TP3 both and in vivo. TP3 at doses of up to 40 μg/ml did not affect the viability of baby hamster kidney cells. Furthermore, TP3 was found to be highly effective at combating peritonitis and wound infection caused by MRSA in mouse models, without inducing adverse behavioral effects or liver or kidney toxicity. TP3 treatment increased survival by 100% at 8 days after infection, and accelerated the progression of proliferation, remodeling, and maturation of infected wounds. Taken together, our results indicate that TP3 enhances the rate of survival of mice infected with the bacterial pathogen MRSA through both antimicrobial and immunomodulatory effects. Overall, these results suggest that TP3 may be suitable for development as a novel topical agent for treatment of infected wounds.

Keywords: Pathology Section; antimicrobial peptides; staphylococcus aureus; tilapia piscidin 3; wound healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Infective Agents / pharmacology*
  • Bacteremia / drug therapy
  • Bacteremia / immunology
  • Bacteremia / microbiology
  • Bacteremia / prevention & control
  • Cricetinae
  • Drug Synergism
  • Female
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Mice
  • Mice, Inbred BALB C
  • Peptide Fragments / pharmacology*
  • Skin / injuries
  • Skin / microbiology
  • Staphylococcal Infections / drug therapy
  • Staphylococcal Infections / immunology
  • Staphylococcal Infections / prevention & control*
  • Staphylococcal Skin Infections / drug therapy
  • Staphylococcal Skin Infections / immunology
  • Staphylococcal Skin Infections / prevention & control
  • Thymopoietins / pharmacology*
  • Wound Healing / drug effects*
  • Wound Healing / immunology
  • Wound Infection / drug therapy
  • Wound Infection / immunology
  • Wound Infection / microbiology
  • Wound Infection / prevention & control*

Substances

  • Anti-Infective Agents
  • Peptide Fragments
  • Thymopoietins
  • splenotritin