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Kutter E.,Evergreen State College | De Vos D.,Burn Wound Center | Gvasalia G.,Tbilisi State Medical University | Alavidze Z.,Eliava Institute of Bacteriophages | And 3 more authors.
Current Pharmaceutical Biotechnology | Year: 2010

Phage therapy is the application of bacteria-specific viruses with the goal of reducing or eliminating pathogenic or nuisance bacteria. While phage therapy has become a broadly relevant technology, including veterinary, agricultural, and food microbiology applications, it is for the treatment or prevention of human infections that phage therapy first caught the world's imagination - see, especially, Arrowsmith by Sinclair Lewis (1925) - and which today is the primary motivator of the field. Nonetheless, though the first human phage therapy took place in the 1920s, by the 1940s the field, was in steep decline despite early promise. The causes were at least three-fold: insufficient understanding among researchers of basic phage biology; over exuberance, which led, along with ignorance, to carelessness; and the advent of antibiotics, an easier to handle as well as highly powerful category of antibacterials. The decline in phage therapy was neither uniform nor complete, especially in the former Soviet Republic of Georgia, where phage therapy traditions and practice continue to this day. In this review we strive toward three goals: 1. To provide an overview of the potential of phage therapy as a means of treating or preventing human diseases; 2. To explore the phage therapy state of the art as currently practiced by physicians in various pockets of phage therapy activity around the world, including in terms of potential commercialization; and 3. To avert a recapitulation of phage therapy's early decline by outlining good practices in phage therapy practice, experimentation, and, ultimately, commercialization. © 2010 Bentham Science Publishers Ltd. Source


Sahota J.S.,University of Leicester | Smith C.M.,University of Leicester | Smith C.M.,University College London | Radhakrishnan P.,University College London | And 7 more authors.
Journal of Aerosol Medicine and Pulmonary Drug Delivery | Year: 2015

Background: The rise in antibiotic-resistant Pseudomonas aeruginosa and the considerable difficulty in eradicating it from patients has re-motivated the study of bacteriophages as a therapeutic option. For this to be effective, host range and viability following nebulization need to be assessed. Host-range has not previously been assessed for the Liverpool Epidemic Strain (LES) isolates that are the most common cystic fibrosis-related clone of P. aeruginosa in the UK. Nebulization studies have not previously been linked to clinically relevant phages. Methods: 84 phenotypically variable isolates of the LES were tested for susceptibility to seven bacteriophages known to have activity against P. aeruginosa. Five of the phages were from the Eliava Institute (IBMV) and 2 were isolated in this study. The viability of the two bacteriophages with the largest host ranges was characterized further to determine their ability to be nebulized and delivered to the lower airways. Phages were nebulized into a cascade impactor and the phage concentration was measured. Results: The bacteriophages tested killed between 66%-98% of the 84 Liverpool Epidemic Strain isolates. Two isolates were multi phage resistant, but were sensitive to most first line anti-Pseudomonal antibiotics. The amount of viable bacteriophages contained in particles that are likely to reach the lower airways (<4.7 μm) was 1% for the Omron and 12% AeroEclipse nebulizer. Conclusions: Individual P. aeruginosa bacteriophages can lyse up to 98% of 84 phenotypically diverse LES strains. High titers of phages can be effectively nebulized. © Copyright 2015, Mary Ann Liebert, Inc. 2015. Source


Zschach H.,Technical University of Denmark | Joensen K.G.,Technical University of Denmark | Lindhard B.,Technical University of Denmark | Lund O.,Technical University of Denmark | And 8 more authors.
Viruses | Year: 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. © 2015 by the authors; licensee MDPI, Basel, Switzerland. Source


Karumidze N.,Eliava Institute of Bacteriophages | Karumidze N.,Ilia State University | Thomas J.A.,University of Maryland, Baltimore | Kvatadze N.,Eliava Institute of Bacteriophages | And 5 more authors.
Applied Microbiology and Biotechnology | Year: 2012

Pseudomonas aeruginosa is an important cause of infections, especially in patients with immunodeficiency or diabetes. Antibiotics are effective in preventing morbidity and mortality from Pseudomonas infection, but because of spreading multidrug-resistant bacterial strains, bacteriophages are being explored as an alternative therapy. Two newly purified broad host range Pseudomonas phages, named vB-Pae-Kakheti25 and vB-Pae-TbilisiM32, were characterized as candidates for use in phage therapy. Morphology, host range, growth properties, thermal stability, serology, genomic sequence, and virion composition are reported. When phages are used as bactericides, they are used in mixtures to overcome the development of resistance in the targeted bacterial population. These two phages are representative of diverse siphoviral and podoviral phage families, respectively, and hence have unrelated mechanisms of infection and no cross-antigenicity. Composing bactericidal phage mixtures with members of different phage families may decrease the incidence of developing resistance through a common mechanism. © Springer-Verlag 2012. Source

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