Safety analysis of a Russian phage cocktail: From MetaGenomic analysis to oral application in healthy human subjects (original) (raw)
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What Can We Learn from a Metagenomic Analysis of a Georgian Bacteriophage Cocktail?
Viruses, 2015
Phage therapy, a practice widespread in Eastern Europe, has untapped potential in the combat against antibiotic-resistant bacterial infections. However, technology transfer to Western medicine is proving challenging. Bioinformatics analysis could help to facilitate this endeavor. In the present study, the Intesti phage cocktail, a key commercial product of the Eliava Institute, Georgia, has been tested on a selection of bacterial strains, sequenced as a metagenomic sample, de novo assembled and analyzed by bioinformatics methods. Furthermore, eight bacterial host strains were infected with the cocktail and the resulting lysates sequenced and compared to the unamplified cocktail. The analysis identified 23 major phage clusters in different abundances in the cocktail, among those clusters related to the ICTV genera T4likevirus, T5likevirus, T7likevirus, Chilikevirus and Twortlikevirus, as well as a cluster that was quite distant to the database sequences and a novel Proteus phage cluster. Examination of the depth of coverage showed the clusters to have different abundances within the cocktail. The cocktail was found to be composed primarily of Myoviridae (35%) and Siphoviridae (32%), with Podoviridae being a minority (15%). No undesirable genes were found.
Applied and Environmental Microbiology, 2007
The complete genome of φEcoM-GJ1, a lytic phage that attacks porcine enterotoxigenic Escherichia coli of serotype O149:H10:F4, was sequenced and analyzed. The morphology of the phage and the identity of the structural proteins were also determined. The genome consisted of 52,975 bp with a G+C content of 44% and was terminally redundant and circularly permuted. Seventy-five potential open reading frames (ORFs) were identified and annotated, but only 29 possessed homologs. The proteins of five ORFs showed homology with proteins of phages of the family Myoviridae , nine with proteins of phages of the family Podoviridae , and six with proteins of phages of the family Siphoviridae . ORF 1 encoded a T7-like single-subunit RNA polymerase and was preceded by a putative E. coli σ 70 -like promoter. Nine putative phage promoters were detected throughout the genome. The genome included a tRNA gene of 95 bp that had a putative 18-bp intron. The phage morphology was typical of phages of the fami...
PHAGE THERAPY: COULD VIRUSES HELP RESOLVE THE WORLDWIDE ANTIBIOTIC CRISIS?
Bacteriophages are bacterio-specific viruses. Involved in the origin of life and evolution,constituting a major part of the biosphere, they are promising as a sustainable,ecological and intrinsically cheap antibacterial. Félix d’Hérelle, one of the discoverers was the first to propose “phage therapy” in the early twentieth century. It was further developed at the Eliava Institute in Tbilisi, Georgia, and used in medical practice in all the previous Soviet Republics until now. The Western world, however, with the advent of antibiotics, forgot about phage therapy. The antibiotic resistance crisis brought back phage therapy as a potential complementary or alternative treatment. The main problem is a lack of evidence-based studies using modern standards as well as the lack of an adapted regulatory framework. Attracting industrial partners and initiating studies in this context is difficult. Phage therapy is sporadically applied under certain conditions like the Helsinki Declaration or specific national regulations (for example, in Poland). This impedes scientific progress and clinical reimplementation. Although several groups have set up animal and human studies, and bacteriophages are already used as antibacterials in the food industry, the clinical reimplementation is lacking while the antibiotic crisis is intensifying worldwide
Exploring phage diversity and potential: Development of phage therapy for bacterial infection
Proceedings of the Annual International Conference Syiah Kuala University Life Sciences Engineering Chapter, 2012
The recent increase in drug-resistance bacteria has become a very serious threat to the treatment of infectious diseases. Over recent decades, a growing numbers of literatures have validated the application of bacteriophages for therapy against antibiotic-resistance bacteria. With rapid dissemination of these resistant bacteria pathogens, the interest in alternative remedies to antibiotics using bacteriophages therapy is gaining new ground. Based on the recent studies of bacteriophage applications against bacterial infections in countries where this alternative therapy has been approved, many scientists and companies believed that phages have the ability to treat and prevent diseases caused by bacteria. Malaysia, being well known as one of the megadiverse countries could promise the potential new phages that could be applied in phage therapy. The overall objectives of this research including isolation and purification of potentially new phages from environments, characterization of the isolated phages based on morphological study, physicochemical attributes, genomic and proteomic analysis. Lastly, the isolated phages would be developed into phage therapy against bacterial infection through in vitro and in vivo test. Preliminary results presented here, show a total of four phages were successfully isolated from human waste. Two of the phages were successfully isolated infecting Proteus mirabilis that caused urinary tract infection in human whereas another two phages infecting Escherichia coli 0157:H7 (caused food-borne diseases) and Escherichia coli ATCC 13706, respectively.
Oral T4-like phage cocktail application to healthy adult volunteers from Bangladesh
Virology, 2012
The genomic diversity of 99 T4-like coliphages was investigated by sequencing an equimolar mixture with Illumina technology and screening them against different databases for horizontal gene transfer and undesired genes. A 9-phage cocktail was given to 15 healthy adults from Bangladesh at a dose of 3 Â 10 9 and 3 Â 10 7 plaque-forming units and placebo respectively. Phages were detected in 64% of the stool samples when subjects were treated with higher titer phage, compared to 30% and 28% with lower-titer phage and placebo, respectively. No Escherichia coli was present in initial stool samples, and no amplification of phage was observed. One percent of the administered oral phage was recovered from the feces. No adverse events were observed by self-report, clinical examination, or from laboratory tests for liver, kidney, and hematology function. No impact of oral phage was seen on the fecal microbiota composition with respect to bacterial 16S rRNA from stool.
Key issues in phage therapy: a report of a dedicated workshop at the viruses of microbes II meeting
Research in Microbiology, 2013
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Escherichia coli (E. coli) is one of the most important causes of gastrointestinal diseases in developing countries. It considered the third cause of diarrhea in children. In this study, bacteriophages were isolated and detected from wastewater against isolates of E. coli by using plaque and spot test assay. Characterized three phages were differed on plaque morphology, particle morphology, host range and titration. According to phage characterization, the three phages were classified into two from Siphoviridae and one from Podoviridae. Combinations of the bacteriophages had broad host range with strong lytic activity against pathogenic E. coli. Phage cocktail revealed high stability at 45°C, pH 9 and 20% of salt concentration. According to the previous characters of a phage cocktail properties can broaden the spectrum of application of phage therapy. Formulated phages were prepared by mixing phages with royal gelly, dried skimmed milk and a mixture of sucrose and corn flour at ratio 1:1(V: W) at phage cocktail concentration 2.2x10 11 plaque forming units (pfu) per mL. These phages formulation remained active for at least 48 days when stored at 4°C in a light protected container with titres of 4.0x10 10 , 3.6x10 10 and 3.4x10 10 pfu/mL for royal gelly, dried skimmed milk and a mixture of corn flour and sucrose respectively.