title: Safety analysis of a Russian phage cocktail: from metagenomic analysis to oral application in healthy human subjects.
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.
authors.affiliation: Nestlé Research Centre, Nestec Ltd, Vers-chez-les-Blanc, CH-1000 Lausanne 26, Switzerland. semccallin@yahoo.com
authors.forename: Shawna
authors.initials: S
authors.lastname: McCallin
authors.forename: Shafiqul
authors.initials: S
authors.lastname: Alam Sarker
authors.forename: Caroline
authors.initials: C
authors.lastname: Barretto
authors.forename: Shamima
authors.initials: S
authors.lastname: Sultana
authors.forename: Bernard
authors.initials: B
authors.lastname: Berger
authors.forename: Sayeda
authors.initials: S
authors.lastname: Huq
authors.forename: Lutz
authors.initials: L
authors.lastname: Krause
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Bibiloni
authors.forename: Bertrand
authors.initials: B
authors.lastname: Schmitt
authors.forename: Gloria
authors.initials: G
authors.lastname: Reuteler
authors.forename: Harald
authors.initials: H
authors.lastname: Brüssow
mesh_terms: D000284:Administration, Oral; D001435:Bacteriophages / Q000145:classification / Q000235:genetics / Q000648:ultrastructure; D001691:Biological Therapy / Q000009:adverse effects* / Q000379:methods*; D004927:Escherichia coli Infections / Q000628:therapy*; D006090:Gram-Negative Bacteria / Q000145:classification / Q000821:virology; D006801:Humans; D056186:Metagenomics / Q000379:methods*; D046529:Microscopy, Electron, Transmission; D017900:Myoviridae / Q000145:classification / Q000235:genetics / Q000648:ultrastructure; D017902:Podoviridae / Q000145:classification / Q000235:genetics / Q000648:ultrastructure; D011512:Proteus Infections / Q000628:therapy*; D012426:Russia; D017906:Siphoviridae / Q000145:classification / Q000235:genetics / Q000648:ultrastructure; D016896:Treatment Outcome
keywords: Bacteriophages; Escherichia coli; Fecal microbiota; Human phage therapy; Metagenomics; Safety