Project: A bacteriophage-based approach to reducing infections caused by antibiotic resistant Escherichia coli

Antibiotic resistance is a significant and increasing problem in many bacterial pathogens that infect animals and humans. Escherichia coli is among the most important of these pathogens, because of its role in intestinal, urinary tract and respiratory disease, and septicaemia in a variety of livestock species, including poultry; and also because many serotypes of E. coli that are associated with extra-intestinal infections in animals and humans are closely related. Antibiotic resistance in E. coli strains is increasing worldwide and this resistance can be maintained even after reducing or withdrawing antibiotic use (Tadesse, 2012). Treatment of E. coli infections in animals and humans thus requires a new and sustainable approach. This consortium will isolate viruses which infect bacteria (bacteriophages, or 'phages') which specifically target surface bacterial determinants of virulence and/or antibiotic resistance transfer. We will isolate phages from the environment, surface water, farms, drains and sewage which are able to infect a range of Avian Pathogenic Escherichia coli (APEC) serotypes. These will be characterised in vitro, and bacteriophage biocontrol candidates will be selected for evaluation in an E. coli septicaemia model in chickens. Selection of the phage will be based on the ability to infect a wide range of pathogenic E. coli strains, in vitro phage replication kinetics, and lack of/minimal host resistance. The potential issue of E. coli resistance to phage infection will be addressed by (i) targeting surface receptors which are important for virulence and/or antibiotic resistance, (ii) the use of cocktails of phages which target different receptors, and (iii) studying the CRISPR-Cas system of wild strains of E. coli to determine its role in phage resistance and its epidemiology and evolution during phage infection. The phage therapy company Ampliphibio is a partner and has collaborated with consortium members for more than 15 years through its UK subsidiary Biocontrol Ltd. This approach can synergise with the development of new drugs and has the potential to provide a sustainable platform for control of antibiotic-resistant pathogens which could easily be extrapolated to many other animal pathogens.

Acronym AntibioPhage
Network ANIHWA
Call 2nd ANIHWA Joint Call

Project partner

Number Name Role Country
French National Institute for Agricultural Research France
University of Leuven Belgium
Ampliphi Biosciences Corporation United States
University of Nottingham Coordinator United Kingdom
University of Copenhagen Denmark