Eliava Institute of Bacteriophage

Tbilisi, Georgia

Eliava Institute of Bacteriophage

Tbilisi, Georgia
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Glonti T.,Eliava Institute of Bacteriophage | Chanishvili N.,Eliava Institute of Bacteriophage
Journal of Applied Microbiology | Year: 2010

Aims: To identify enzymes associated with bacteriophages infecting cystic fibrosis (CF) strains of Pseudomonas aeruginosa that are able to degrade extracellular alginic acids elaborated by the host bacterium. Methods and Results: Plaques produced by 21 Ps. aeruginosa-specific phages were screened for the presence of haloes, an indicator of capsule hydrolytic activity. Four phages produced haloed plaques, and one (PT-6) was investigated further. PT-6 was shown by electron microscopy to belong to Podoviridae family C1, to reduce the viscosity of four alginate preparations using a rolling ball viscometer and to release uronic acid-containing fragments from the polymers, as judged by spectrophotometry and thin layer chromatography. The alginase was partially purified by gel filtration chromatography and shown to be a 37 kDa polypeptide. Conclusions: Infection of CF strains of Ps. aeruginosa by phage PT-6 involves hydrolysis of the exopolysaccharide secreted by the host. Significance and Impact of the Study: The alginase produced by PT-6 has the potential to increase the well-being of CF suffers by improving the surface properties of sputum, accelerating phagocytic uptake of bacteria and perturbing bacterial growth in biofilms. © 2009 The Society for Applied Microbiology.

Merabishvili M.,Queen Astrid Military Hospital | Merabishvili M.,Ghent University | Merabishvili M.,Eliava Institute of Bacteriophage | Vervaet C.,Ghent University | And 6 more authors.
PLoS ONE | Year: 2013

Staphylococcus aureus phage ISP was lyophilized, using an Amsco-Finn Aqua GT4 freeze dryer, in the presence of six different stabilizers at different concentrations. Stability of the lyophilized phage at 4°C was monitored up to 37 months and compared to stability in Luria Bertani broth and physiological saline at 4°C. Sucrose and trehalose were shown to be the best stabilizing additives, causing a decrease of only 1 log immediately after the lyophilization procedure and showing high stability during a 27 month storage period. © 2013 Merabishvili et al.

Toklikishvili N.,Hebrew University of Jerusalem | Toklikishvili N.,Eliava Institute of Bacteriophage | Dandurishvili N.,Hebrew University of Jerusalem | Dandurishvili N.,Khanchaveli Institute of Plant Protection | And 7 more authors.
Plant Pathology | Year: 2010

This study showed that various rhizosphere bacteria producing the enzyme 1-aminocyclopropane-1-carboxylate (ACC) deaminase (ACCD), which can degrade ACC, the immediate precursor of ethylene in plants, and thereby lower plant ethylene levels, can act as promising biocontrol agents of pathogenic strains of Agrobacterium tumefaciens and A. vitis. Soaking the roots of tomato (Solanum lycopersicum) seedlings in a suspension of the ACCD-producing Pseudomonas putida UW4, Burkholderia phytofirmans PsJN or Azospirillum brasilense Cd1843 transformed by plasmid pRKTACC carrying the ACCD-encoding gene acdS from UW4, significantly reduced the development of tumours on tomato plants injected 4-5 days later with pathogenic Agrobacterium strains via wounds on the plant stem. The fresh mass of tumours formed by plants pretreated with ACCD-producing strains was typically four- to fivefold less than that of tumours formed on control plants inoculated only with a pathogenic Agrobacterium strain. Simultaneously, the level of ethylene evolution per amount of tumour mass on plants pretreated with ACCD-producing bacteria decreased four to eight times compared with that from tumours formed on control plants or plants pretreated with bacteria deficient in ACCD production. Moreover, transgenic tomato plants expressing a bacterial ACCD were found to be highly resistant to crown gall formation relative to the parental, non-transformed tomato plants. The results support the hypothesis that ethylene is a crucial factor in Agrobacterium tumour formation, and that ACCD-produced rhizosphere bacteria may protect plants infected by pathogenic Agrobacteria from crown gall disease. No claim to original US government works. Plant Pathology © 2010 BSPP.

Rose T.,Queen Astrid Military Hospital | Verbeken G.,Queen Astrid Military Hospital | de Vos D.,Queen Astrid Military Hospital | Merabishvili M.,Queen Astrid Military Hospital | And 7 more authors.
International Journal of Burns and Trauma | Year: 2014

Antibiotic resistance has become a major public health problem and the antibiotics pipeline is running dry. Bacteriophages (phages) may offer an ‘innovative’ means of infection treatment, which can be combined or alternated with antibiotic therapy and may enhance our abilities to treat bacterial infections successfully. Today, in the Queen Astrid Military Hospital, phage therapy is increasingly considered as part of a salvage therapy for patients in therapeutic dead end, particularly those with multidrug resistant infections. We describe the application of a well-defined and quality controlled phage cocktail, active against Pseudomonas aeruginosa and Staphylococcus aureus, on colonized burn wounds within a modest clinical trial (nine patients, 10 applications), which was approved by a leading Belgian Medical Ethical Committee. No adverse events, clinical abnormalities or changes in laboratory test results that could be related to the application of phages were observed. Unfortunately, this very prudent ‘clinical trial’ did not allow for an adequate evaluation of the efficacy of the phage cocktail. Nevertheless, this first ‘baby step’ revealed several pitfalls and lessons for future experimental phage therapy and helped overcome the psychological hurdles that existed to the use of viruses in the treatment of patients in our burn unit. © 2014, E-Century Publishing Corporation. All rights reserved.

Trupschuch S.,Robert Koch Institute | Laverde Gomez J.A.,Robert Koch Institute | Ediberidze I.,Eliava Institute of Bacteriophage | Flieger A.,Robert Koch Institute | Rabsch W.,Robert Koch Institute
International Journal of Medical Microbiology | Year: 2010

In 2006, monophasic, multidrug-resistant Salmonella enterica spp. enterica serovar 4,[5],12:i:- strains appeared as a novel serotype in Germany, associated with large diffuse outbreaks and increased need for hospitalisation. The emerging 4,[5],12:i:- strains isolated from patients in Germany belong mainly to phage type DT193 according to the Anderson phage typing scheme for S. Typhimurium (STM) and exhibit at least a tetra-drug resistance. The strains have been shown to harbour STM-specific Gifsy-1, Gifsy-2, and ST64B prophages. Furthermore, the extensive sequence similarity of the tRNA regions between one characterised 4,[5],12:i:- phage type DT193 and the S. Typhimurium LT2 strain as well as the STM-specific position of an IS200 element within the fliA-fliB intergenic region (Echeita et al., 2001) prompted us to classify them as a monophasic variant of S. Typhimurium. In 2008, the monophasic variant represented 42.2% of all S. Typhimurium isolates from human analysed at the National Reference Centre. Searching for insertions in tRNA sites resulted in the detection of an 18.4-kb fragment adjacent to the thrW tRNA locus, exhibiting a lower G+C content compared to the LT2 genome. Sequence analysis identified 17 potential ORFs. Some of them showed high similarity to enterobacterial phage sequences and sequences from Shigella boydii, Sh. dysenteriae, avian pathogenic Escherichia coli and other Escherichia spp. The biological function of this novel island with respect to virulence properties and metabolic functions is under investigation. © 2010 Elsevier GmbH. All rights reserved.

Chanishvili N.,Eliava Institute of Bacteriophage
NATO Science for Peace and Security Series A: Chemistry and Biology | Year: 2011

This review describes the use of bacteriophages against bacterial infections in the battlefield and protection of the civilian population. High therapeutic and protective potential of bacteriophages suggests that they could be an efficient means against bio-terrorist attacks. © 2011 Springer Science+Business Media B.V.

Vandersteegen K.,Catholic University of Leuven | Mattheus W.,Catholic University of Leuven | Ceyssens P.-J.,Catholic University of Leuven | Bilocq F.,Queen Astrid Military Hospital | And 8 more authors.
PLoS ONE | Year: 2011

The increasing antibiotic resistance in bacterial populations requires alternatives for classical treatment of infectious diseases and therefore drives the renewed interest in phage therapy. Methicillin resistant Staphylococcus aureus (MRSA) is a major problem in health care settings and live-stock breeding across the world. This research aims at a thorough microbiological, genomic, and proteomic characterization of S. aureus phage ISP, required for therapeutic applications. Host range screening of a large batch of S. aureus isolates and subsequent fingerprint and DNA microarray analysis of the isolates revealed a substantial activity of ISP against 86% of the isolates, including relevant MRSA strains. From a phage therapy perspective, the infection parameters and the frequency of bacterial mutations conferring ISP resistance were determined. Further, ISP was proven to be stable in relevant in vivo conditions and subcutaneous as well as nasal and oral ISP administration to rabbits appeared to cause no adverse effects. ISP encodes 215 gene products on its 138,339 bp genome, 22 of which were confirmed as structural proteins using tandem electrospray ionization-mass spectrometry (ESI-MS/MS), and shares strong sequence homology with the 'Twort-like viruses'. No toxic or virulence-associated proteins were observed. The microbiological and molecular characterization of ISP supports its application in a phage cocktail for therapeutic purposes. © 2011 Vandersteegen et al.

Chanishvili N.,Eliava Institute of Bacteriophage
Advances in Virus Research | Year: 2012

Felix d'Herelle proposed the use of bacteriophages for the therapy of human and animal bacterial infections at the beginning of the 20th century. This approach, however, was not widely accepted in the West. After the emergence of antibiotics in 1940s, phage research was diverted to a more fundamental level. At the same time, phage therapy was widely practiced in the Soviet Union due to collaboration of Felix d'Herelle with his Georgian colleagues. The majority of the articles dedicated to this subject are from the 1930s and 1940s. The old Soviet literature indicates that phage therapy was used extensively to treat a wide range of bacterial infections in the areas of dermatology (Beridze, 1938), ophthalmology (Rodigina, 1938), urology (Tsulukidze, 1938), stomatology (Ruchko and Tretyak, 1936), pediatrics (Alexandrova et al., 1935; Lurie, 1938), otolaryngology (Ermolieva, 1939), and surgery (Tsulukidze, 1940, 1941). These articles were published in Russian and thus were not readily available to Western scientists. The Western skepticism toward phage therapy itself was again followed by renewed interest and reappraisal, mainly due to the emergence of drug-resistant bacteria. Often the experiments described in the old Soviet articles were not designed properly: the use of placebos and the coding of preparations were absent from most of the studies, number of patients in the experimental and control groups was unequal or missing, sometimes no control groups were used at all, or patients treated previously unsuccessfully with antibiotics were employed as an experimental group and as control. The results obtained and the efficiency of phage prophylaxis were estimated by comparing with results obtained in previous years. In most publications, phage titers and descriptions of methods used for evaluation of the results are not specified. Nevertheless, past experience indicates some effectiveness of phage therapy and prophylaxis. Therefore, these clinical results should not be neglected when designing any future studies. © 2012 Elsevier Inc.

PubMed | Eliava Institute of Bacteriophage
Type: Journal Article | Journal: Current drug delivery | Year: 2016

Bacteriophage (from bacteria and Greek phagein to devour or bacterial eaters) are bacterial viruses that infect and kill bacteria. Bacteriophages (shortly phages) are among the most common and diverse entities in the biosphere. The estimated number of phages on earth is about 1032. Bacteriophages are often isolated from environmental sources, such as water samples, etc. Felix dHerelle, one of the discoverers of bacteriophages, was the one who suggested them for therapy of human and animal bacterial infections. This idea was very popular in the world until the advent of antibiotics commercial after which production of therapeutic phages ceased in most of the Western countries, but not in the former Soviet Union. The application of antibiotics in the clinical practice, besides the well-known side effects, entails, in addition, the appearance of the forms of bacteria, resistant to newly synthesized preparations. It was concluded that a European and global strategy to address this gap is urgently needed. Now, faced with the alarming growth of a variety of antibiotic resistant bacterial infections, Western researchers and governments are giving phages a serious look. The phages nowadays are seen as a possible therapy against multi-drug-resistant strains of many bacteria. The therapeutic action of bacteriophages significantly differs from antibiotics, which makes them still active against multi-drug-resistant bacteria. Bacteriophages have a number of other advantages in comparison with antibiotics. First of all, they are efficient against multi-drug-resistant bacteria. The aim of this review was to provide an overview of the past and current experiences in the field of phage therapy in the countries where it has been traditionally applied in the clinical practice. Although the style and quality of old Soviet scientific publications dedicated to phage therapy are not challenging the international standards, there is still valuable information which may not be neglected by modern researchers. This information is especially important as it remained unavailable for the Western scientists before because of the language barriers until now. The goal of this article is to encourage further research on this topic, and facilitate rapid decisions on the development of appropriate regulations, which would ultimately permit the use of phages as therapeutic or preventative medicines in daily clinical practice in the Western countries where multiplying drug-resistant bacteria gradually becomes the greatest life threatening problem.

Merabishvili M.,Queen Astrid Military Hospital | Merabishvili M.,Eliava Institute of Bacteriophage | Merabishvili M.,Ghent University | de Vos D.,Queen Astrid Military Hospital | And 14 more authors.
PLoS ONE | Year: 2012

In 2011, a novel strain of O104:H4 Escherichia coli caused a serious outbreak of foodborne hemolytic uremic syndrome and bloody diarrhea in Germany. Antibiotics were of questionable use and 54 deaths occurred. Candidate therapeutic bacteriophages that efficiently lyse the E. coli O104:H4 outbreak strain could be selected rather easily from a phage bank or isolated from the environment. It is argued that phage therapy should be more considered as a potential armament against the growing threat of (resistant) bacterial infections. © 2012 Merabishvili et al.

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