Safety analysis of a Russian phage cocktail: From MetaGenomic analysis to oral application in healthy human subjects

• Published in: Virology (New York, N.Y.) N.Y.), 2013-09, Vol.443 (2), p.187-196
• Main Authors: McCallin, Shawna, Alam Sarker, Shafiqul, Barretto, Caroline, Sultana, Shamima, Berger, Bernard, Huq, Sayeda, Krause, Lutz, Bibiloni, Rodrigo, Schmitt, Bertrand, Reuteler, Gloria, Brüssow, Harald
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Administration, Oral; BACTERIOPHAGES; Bacteriophages - classification; Bacteriophages - genetics; Bacteriophages - ultrastructure; Biological Therapy - adverse effects; Biological Therapy - methods; CLINICAL TRIALS; CONTIGS; EASTERN EUROPE; ELECTRON MICROSCOPY; ESCHERICHIA COLI; Escherichia coli Infections - therapy; Fecal microbiota; GENES; Gram-Negative Bacteria - classification; Gram-Negative Bacteria - virology; Human phage therapy; Humans; Infectious Disease; Metagenomics; Metagenomics - methods; Microscopy, Electron, Transmission; Myoviridae; Myoviridae - classification; Myoviridae - genetics; Myoviridae - ultrastructure; Myovirus; Podoviridae; Podoviridae - classification; Podoviridae - genetics; Podoviridae - ultrastructure; PROTEUS; Proteus Infections - therapy; Russia; Safety; SAFETY ANALYSIS; Siphoviridae; Siphoviridae - classification; Siphoviridae - genetics; Siphoviridae - ultrastructure; THERAPY; Treatment Outcome
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2013.05.022

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.