Introduction
Bacteriophage therapy can be developed to target emerging diarrhoeal pathogens, but doing so in the absence of microbiome disruption, which occurs with antibiotic treatment, has not been established.
Aim
Identify a therapeutic bacteriophage that kills diarrhoeagenic enteroaggregative
Escherichia coli
(EAEC) while leaving the human microbiome intact.
Methodology
Phages from wastewater in Portland, OR, USA were screened for bacteriolytic activity by overlay assay. One isolated phage,
PDX
, was classified by electron microscopy and genome sequencing. A mouse model of infection determined whether the phage was therapeutic against EAEC. 16S metagenomic analysis of anaerobic cultures determined whether a normal human microbiome was altered by treatment.
Results
Escherichia
virus
PDX
, a member of the strictly lytic family
Myoviridae
, killed a case-associated EAEC isolate from a child in rural Tennessee in a dose-dependent manner, and killed EAEC isolates from Columbian children. A single dose of
PDX
(multiplicity of infection: 100) 1 day post-infection reduced EAEC recovered from mouse faeces.
PDX
also killed EAEC when cultured anaerobically in the presence of human faecal bacteria. While the addition of EAEC reduced the β-diversity of the human microbiota, that of the cultures with either faeces alone, faeces with EAEC and
PDX
, or with just
PDX
phage was not different statistically.
Conclusion
PDX
killed EAEC isolate EN1E-0007
in vivo
and
in vitro
, while not altering the diversity of normal human microbiota in anaerobic culture, and thus could be part of an effective therapy for children in developing countries and those suffering from EAEC-mediated traveller’s diarrhoea without causing dysbiosis.