Third Call

  • Call is closed
  • 20 funding organisations involved from 16 countries
  • Total budget of ca. 9.5 Mio €
  • 39 full proposals received
  • 12 projects recommended for funding

BLAAT

 

Bacteriophage lysins as  alternatives to antimicrobial treatment 

 

Topic:

Production diseases (Topic 2)

Duration of project:

36 Months

Total project costs:

1.053.476€

Animal group:

Pigs

Principle investigator:

Prof. Karl Pedersen, Technical University of Denmark (DTU-VET), Denmark

Project partner:

KU Leuven (KUL), Belgium
Agencia Estatal Consejo Superior de Investigacione s Cientificas (IPLA-CSIC), Spain
Stockholm University (SU), Sweden
Queen Astrid Military Hospital (LabMCT-QAMH/RMA), Belgium
Universidad de Alicante (UA), Spain

Abstract:

The main goal of this proposal is to explore the potential of bacteriophage lysins as alternatives to antibiotics in animal production. These bacteriophage-encoded enzymes are capable of highly specific, efficient and rapid degradation of bacterial peptidoglycan leading to cell lysis and death irrespectively of the physiological state. Until recently the killing range of lysins was limited to Gram-positive bacteria. We elaborated a strategy to target Gram-negative pathogens as well. In another development, we discovered that certain lysins from Staphylococcus aureus phages and the corresponding constructs display multiple catalytic activities, with very low probability of resistance development. These findings open a promising avenue to control and treat a wide range of animal and human bacterial infections. In this project, we will investigate the therapeutic potential of lysins against Gram-positive (S. aureus MRSA CC398) and Gram-negative (enterotoxigenic Escherichia coli, ETEC) bacteria that represent important zoonotic and disease-causing pathogens in pigs. The former is increasingly recognized as an emerging zoonotic pathogen, while ETEC causes a considerable morbidity and mortality in the pre- and post-weaning pigs.

The main activities in this project include: creating a collection of bacteriophages targeting these two important pathogens; rigorous functional and structural analyses of phages in the collection; identification, cloning, detailed analysis and engineering of lysin genes; pilot studies to evaluate the antimicrobial activity of lysin preparations in pigs.

Implementation of this project will result in antibiotic alternative that: does not select for antibiotic resistance, limit the evolution and spread of antibiotic resistance, selectively eliminates multidrug-resistant (MDR) pathogens, decrease the pathogenicity and antimicrobial resistance gene pool thus preventing the emergence of novel MDR pathogens, and does not affect commensal microbiota. The proof of concept obtained can be implemented for other animal species and directed against other MDR bacterial pathogens infecting animals and humans. Thus the project addresses many aspects the One Health initiative as well.

 

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