Safety analysis of a Russian phage cocktail: from metagenomic analysis to oral application in healthy human subjects

Virology. 2013 Sep 1;443(2):187-96. doi: 10.1016/j.virol.2013.05.022. Epub 2013 Jun 10.

Abstract

Phage therapy has a long tradition in Eastern Europe, where preparations are comprised of complex phage cocktails whose compositions have not been described. We investigated the composition of a phage cocktail from the Russian pharmaceutical company Microgen targeting Escherichia coli/Proteus infections. Electron microscopy identified six phage types, with numerically T7-like phages dominating over T4-like phages. A metagenomic approach using taxonomical classification, reference mapping and de novo assembly identified 18 distinct phage types, including 7 genera of Podoviridae, 2 established and 2 proposed genera of Myoviridae, and 2 genera of Siphoviridae. De novo assembly yielded 7 contigs greater than 30 kb, including a 147-kb Myovirus genome and a 42-kb genome of a potentially new phage. Bioinformatic analysis did not reveal undesired genes and a small human volunteer trial did not associate adverse effects with oral phage exposure.

Keywords: Bacteriophages; Escherichia coli; Fecal microbiota; Human phage therapy; Metagenomics; Safety.

Publication types

  • Clinical Trial

MeSH terms

  • Administration, Oral
  • Bacteriophages* / classification
  • Bacteriophages* / genetics
  • Bacteriophages* / ultrastructure
  • Biological Therapy / adverse effects*
  • Biological Therapy / methods*
  • Escherichia coli Infections / therapy*
  • Gram-Negative Bacteria / classification
  • Gram-Negative Bacteria / virology
  • Humans
  • Metagenomics / methods*
  • Microscopy, Electron, Transmission
  • Myoviridae / classification
  • Myoviridae / genetics
  • Myoviridae / ultrastructure
  • Podoviridae / classification
  • Podoviridae / genetics
  • Podoviridae / ultrastructure
  • Proteus Infections / therapy*
  • Russia
  • Siphoviridae / classification
  • Siphoviridae / genetics
  • Siphoviridae / ultrastructure
  • Treatment Outcome