Antibiofilm Activity of a Broad-Range Recombinant Endolysin LysECD7: In Vitro and In Vivo Study

Viruses. 2020 May 15;12(5):545. doi: 10.3390/v12050545.

Abstract

Surfaces of implanted medical devices are highly susceptible to biofilm formation. Bacteria in biofilms are embedded in a self-produced extracellular matrix that inhibits the penetration of antibiotics and significantly contributes to the mechanical stability of the colonizing community which leads to an increase in morbidity and mortality rate in clinical settings. Therefore, new antibiofilm approaches and substances are urgently needed. In this paper, we test the efficacy of a broad-range recombinant endolysin of the coliphage LysECD7 against forming and mature biofilms. We used a strong biofilm producer-Klebsiella pneumoniae Ts 141-14 clinical isolate. In vitro investigation of the antibacterial activity was performed using the standard biofilm assay in microtiter plates. We optimized the implantable diffusion chamber approach in order to reach strong biofilm formation in vivo avoiding severe consequences of the pathogen for the animals and to obtain a well-reproducible model of implant-associated infection. Endolysin LysECD7 significantly reduced the biofilm formation and was capable of degrading the preformed biofilm in vitro. The animal trials on the preformed biofilms confirmed these results. Overall, our results show that LysECD7 is a promising substance against clinically relevant biofilms.

Keywords: animal trial; biofilm degradation; drug-resistant bacteria; endolysin; implant-associated infection model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / isolation & purification
  • Anti-Bacterial Agents / pharmacology*
  • Biofilms / drug effects*
  • Biofilms / growth & development
  • Coliphages / enzymology
  • Coliphages / genetics
  • Disease Models, Animal
  • Drug Resistance, Multiple, Bacterial
  • Endopeptidases / administration & dosage
  • Endopeptidases / genetics
  • Endopeptidases / isolation & purification
  • Endopeptidases / pharmacology*
  • Female
  • Klebsiella Infections / microbiology
  • Klebsiella Infections / prevention & control
  • Klebsiella pneumoniae / drug effects*
  • Klebsiella pneumoniae / physiology
  • Microbial Sensitivity Tests
  • Prosthesis-Related Infections / microbiology
  • Prosthesis-Related Infections / prevention & control
  • Rats
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / genetics
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / pharmacology

Substances

  • Anti-Bacterial Agents
  • Recombinant Proteins
  • Endopeptidases
  • endolysin