AUTHOR=Baig Abiyad , Colom Joan , Barrow Paul , Schouler Catherine , Moodley Arshnee , Lavigne Rob , Atterbury Robert , Atterbury Robert , Barrow Paul , Baig Abiyad , Christensen Jens Peter , Moodley Arshnee , Jakociune Dziuginta , Schouler Catherine , Lavigne Rob , Wagemans Jeroen 

TITLE=Biology and Genomics of an Historic Therapeutic Escherichia coli Bacteriophage Collection

JOURNAL=Frontiers in Microbiology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2017.01652

DOI=10.3389/fmicb.2017.01652

ISSN=1664-302X

ABSTRACT=<p>We have performed microbiological and genomic characterization of an historic collection of nine bacteriophages, specifically infecting a K1 <italic>E. coli</italic> O18:K1:H7 ColV<sup>+</sup> strain. These phages were isolated from sewage and tested for their efficacy <italic>in vivo</italic> for the treatment of systemic <italic>E. coli</italic> infection in a mouse infection model by <xref ref-type="bibr" rid="B34">Smith and Huggins (1982)</xref>. The aim of the study was to identify common microbiological and genomic characteristics, which co-relate to the performance of these phages in <italic>in vivo</italic> study. These features will allow an informed selection of phages for use as therapeutic agents. Transmission electron microscopy showed that six of the nine phages were <italic>Podoviridae</italic> and the remaining three were <italic>Siphoviridae</italic>. The four best performing phages <italic>in vivo</italic> belonged to the <italic>Podoviridae</italic> family. <italic>In vitro</italic>, these phages exhibited very short latent and rise periods in our study. In agreement with their microbiological profiles, characterization by genome sequencing showed that all six podoviruses belong to the <italic>Autographivirinae</italic> subfamily. Of these, four were isolates of the same species (99% identity), whereas two had divergent genomes compared to other podoviruses. The <italic>Siphoviridae</italic> phages, which were moderate to poor performers <italic>in vivo</italic>, exhibited longer latent and rise periods <italic>in vitro</italic>. Two of the three siphoviruses were closely related to each other (99% identity), but all can be associated with the <italic>Guernseyvirinae</italic> subfamily. Genome sequence comparison of both types of phages showed that a gene encoding for DNA-dependent RNA polymerase was only present in phages with faster replication cycle, which may account for their better performance <italic>in vivo</italic>. These data define a combination of microbiological, genomic and <italic>in vivo</italic> characteristics which allow a more rational evaluation of the original <italic>in vivo</italic> data and pave the way for the selection of phages for future phage therapy trails.</p>