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A Mouse Model to Assess Innate Immune Response to Staphylococcus aureus Infection
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A Mouse Model to Assess Innate Immune Response to Staphylococcus aureus Infection

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Evolutionarily distinct bacteriophage endolysins featuring conserved peptidoglycan cleavage sites protect mice from

Mathias Schmelcher1, Yang Shen2, Daniel C Nelson3

  • 1Animal Biosciences and Biotechnology Laboratory, ANRI, NEA, ARS, USDA, 10300 Baltimore Ave., Beltsville, MD 20705-2350, USA Institute of Food, Nutrition and Health, ETH Zurich, Schmelzbergstrasse 7, 8092 Zurich, Switzerland mathias.schmelcher@hest.ethz.ch.

The Journal of Antimicrobial Chemotherapy
|January 30, 2015
PubMed
Abstract

Insights

Bacteriophage endolysins (PGHs) show significant antimicrobial activity against Staphylococcus aureus, including drug-resistant strains and biofilms. Six PGHs provided complete protection in a mouse model, highlighting their potential for treating S. aureus infections.

Area of Science:

  • Microbiology
  • Biochemistry
  • Molecular Biology

Background:

  • Increasing antibiotic resistance in Staphylococcus aureus necessitates novel therapeutic strategies.
  • Bacteriophage endolysins (peptidoglycan hydrolases, PGHs) are emerging as potent antimicrobial agents.
  • PGHs target the conserved staphylococcal peptidoglycan layer.

Purpose of the Study:

  • To evaluate the antimicrobial activity of nine distinct staphylococcal PGHs.
  • To characterize the biochemical properties and cleavage specificities of these PGHs.
  • To assess the efficacy of PGHs against S. aureus biofilms and systemic infections.

Main Methods:

  • Recombinant expression and purification of nine PGHs.
  • In vitro lytic activity assays (zymogram, turbidity reduction, plate lysis) against diverse S. aureus and CoNS strains.
  • Biochemical determination of PGH cleavage sites and MS analysis.
  • Efficacy testing against S. aureus biofilms and in a murine model of MRSA infection.

Main Results:

  • PGHs exhibited varying in vitro lytic activities against a broad spectrum of staphylococcal strains, including resistant and cell surface mutants.
  • All tested PGHs were effective against static S. aureus biofilms.
  • Six out of nine PGHs achieved 100% protection in a mouse model of systemic MRSA infection.

Conclusions:

  • PGHs demonstrate significant potential as therapeutic agents against S. aureus infections.
  • Despite conserved peptidoglycan targets, the enzymes display diverse antimicrobial and biochemical properties.
  • The findings suggest broad applicability of PGHs in combating staphylococcal infections.
Keywords:
antibiotic resistanceantimicrobialbiofilmpeptidoglycan hydrolase

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