A bacteriophage-based approach to reducing infections caused by antibiotic resistant Escherichia coli – AntibioPhage

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.