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Phage therapy is the therapeutic use of lytic bacteriophages to treat pathogenic bacterial infections. Bacteriophages, or "phages" are viruses that invade only bacterial cells and, in the case of lytic phages, cause the bacterium to burst and die, thus releasing more phages. Phage therapy is one of the viable alternatives to antibiotics, being developed for clinical use in the 21st century by many research groups in Europe and the US. After having been extensively used and developed mainly in former Soviet Union countries for about 90 years, phage therapy is now becoming more available in other countries such as USA for a variety of bacterial and poly-microbial biofilm infections.[1] Phage therapy has many applications in human medicine as well as dentistry, veterinary science and agriculture. Image File history File links Trialphage. ...
Image File history File links Trialphage. ...
A bacteriophage (from bacteria and Greek phagein, to eat) is a virus that infects bacteria. ...
Phyla/Divisions Actinobacteria Aquificae Bacteroidetes/Chlorobi Chlamydiae/Verrucomicrobia Chloroflexi Chrysiogenetes Cyanobacteria Deferribacteres Deinococcus-Thermus Dictyoglomi Fibrobacteres/Acidobacteria Firmicutes Fusobacteria Gemmatimonadetes Nitrospirae Omnibacteria Planctomycetes Proteobacteria Spirochaetes Thermodesulfobacteria Thermomicrobia Thermotogae Bacteria (singular, bacterium) are a major group of living organisms. ...
This article is about the biological definition of the word Lysis. ...
A bacteriophage (from bacteria and Greek phagein, to eat) is a virus that infects bacteria. ...
Staphylococcus aureus - Antibiotics test plate. ...
An important benefit of phage therapy is that bacteriophages can be much more specific than more common drugs, so can be chosen to be harmless to not only the host organism (human, animal or plant), but also other beneficial bacteria, such as gut flora, reducing chance for opportunistic infections. They also have few if any side effects as opposed to drugs, and do not stress the liver. Because they replicate in vivo, a single, small dose is sometimes sufficient. On the other hand this specificity is also a disadvantage, a phage will only kill a bacterium if it is a match to the specific subspecies; thus phage mixtures are often applied to improve the chances of success, or samples can be taken and an appropriate phage identified. Escherichia coli, one of the many species of bacteria present in the human gut. ...
Opportunistic infections are infections in immunodeficient patients caused by pathogens which are incapable of causing infection in immunocompetent individuals. ...
In vivo (Latin for (with)in the living). ...
Phages are currently being used therapeutically to treat bacterial infections that do not respond to conventional antibiotics. They tend to be more successful where there is a biofilm covered by a polysaccharide layer, that antibiotics typically cannot penetrate. Other biofilms include those on medical instruments, so an enzyme added to a phage can effectively selectively wipe out even bacteria beneath these films, which is impossible currently in Western medicine. [2] Staphylococcus aureus biofilm on an indwelling catheter. ...
Polysaccharides (sometimes called glycans) are relatively complex carbohydrates. ...
History Following the discovery of bacteriophages by Frederick Twort and Felix d'Hérelle in 1915 and 1917, phage therapy was immediately recognized by many to be a key way forward for the eradication of bacterial infections. A Georgian, George Eliava, was making similar discoveries. He travelled to the Pasteur Institute in Paris where he met d'Hérelle, and in 1926 he founded an Institute in Tbilisi, Georgia devoted to the development of phage therapy. This article belongs in one or more categories. ...
Félix dHerelle (April 25, 1873 – February 22, 1949) was a French-Canadian microbiologist, one of the discoverers of bacteriophages (small viruses that only attack and kill bacteria), and inventor of phage therapy. ...
In neighbouring countries including Russia, extensive research and development soon began in this field. In the USA during the 1940s, commercialization of phage therapy was undertaken by the large pharmaceutical company, Eli Lilly. Eli Lilly and Company (NYSE: LLY) is a global pharmaceutical company and one of the worlds largest corporations. ...
Whilst knowledge was being accumulated regarding the biology of phages and how to use phage cocktails correctly, early uses of phage therapy were often unreliable. When antibiotics were discovered in 1941 and marketed widely in the USA and Europe, Western scientists mostly lost interest in further use and study of phage therapy for some time. An antibiotic is a drug that kills or slows the growth of bacteria. ...
Isolated from Western advances in antibiotic production in the 1940s, Russian scientists continued to develop already successful phage therapy to treat the wounds of soldiers in field hospitals. During World War II, the Soviet Union used bacteriophages to treat many soldiers infected with various bacterial diseases e.g. dysentery and gangrene. The success rate was as good as, if not better than any antibiotic.[citation needed] Russian researchers continued to develop and to refine their treatments and to publish their research and results. However, due to the scientific barriers of the Cold War, this knowledge was not translated and did not proliferate across the world. This article is about a military rank. ...
47th Combat Support Hospital, 2000 A field hospital is a large mobile medical unit that temporarily takes care of casualties on-site before they can be safely transported to more permanent hospital facilities. ...
Combatants Allied powers: China France Great Britain Soviet Union United States and others Axis powers: Germany Italy Japan and others Commanders Chiang Kai-shek Charles de Gaulle Winston Churchill Joseph Stalin Franklin Roosevelt Adolf Hitler Benito Mussolini Hideki TÅjÅ Casualties Military dead: 17,000,000 Civilian dead: 33,000...
For other uses, see Cold War (disambiguation). ...
There is an extensive library and research center at the Eliava Institute in Tbilisi, Georgia. Phage therapy is today a widespread form of treatment in neighbouring countries. For 80 years Georgian doctors have been treating local people including babies and newborns with phages. "Phages will kill bacteria completely but only if they are matched well."[3] The tone or style of this article or section may not be appropriate for Wikipedia. ...
As a result of the development of antibiotic resistance since the 1950s and an advancement of scientific knowledge, there is renewed interest worldwide in the ability of phage therapy to eradicate bacterial infections and chronic polymicrobial biofilm, along with other strategies.
Phages have been explored as means to eliminate pathogens like Campylobacter in raw food and Listeria in fresh food or to reduce food spoilage bacteria.[4] In agricultural practice phages were used to fight pathogens like Campylobacter, Escherichia and Salmonella in farm animals, Lactococcus and Vibrio pathogens in fish from aquaculture and Erwinia and Xanthomonas in plants of agricultural importance. The oldest use was, however, in human medicine. Phages were used against diarrheal diseases caused by E. coli, Shigella or Vibrio and against wound infections caused by facultative pathogens of the skin like staphylococci and streptococci. Recently the phage therapy approach has been applied to systemic and even intracellular infections and the addition of non-replicating phage and isolated phage enzymes like lysins to the antimicrobial arsenal. However, definitive proof for the efficiency of these phage approaches in the field or the hospital is only provided in a few cases.[4] Species C. fetus C. jejuni Campylobacter is a genus of Gram-negative bacteria. ...
Species Listeria monocytogenes Listeria ivanovii Listeria innocua Listeria welshimeri Listeria seegligeri Listeria grayi Listeria innocua Listeria is a bacterial genus containing six species. ...
Species C. fetus C. jejuni Campylobacter is a genus of Gram-negative bacteria. ...
Escherichia - Wikipedia /**/ @import /skins/monobook/IE50Fixes. ...
Species Salmonella bongori Salmonella enterica Salmonella arizonae Salmonella enteritidis Salmonella typhi Salmonella typhimurium Salmonella is a genus of rod-shaped Gram-negative enterobacteria that causes typhoid fever, paratyphoid fever, and foodborne illness. ...
Species Lactococcus garvieae Lactococcus lactis Lactococcus piscium Lactococcus plantarum Lactococcus raffinolactis Lactococcus is the genus of bacteria formerly known as Streptococcus Group N and related species. ...
Vibrio is a genus of bacteria, included in the gamma subgroup of the Proteobacteria. ...
Species Candidatus Erwinia dacicola Erwinia amylovora Erwinia aphidicola Erwinia billingiae Erwinia chrysantum Erwinia mallotivora Erwinia papayae Erwinia persicina Erwinia psidii Erwinia pyrifoliae Erwinia rhapontici Erwinia toletana Erwinia tracheiphila Erwinia is a genus of Enterobacteriaceae bacteria containing mostly plant pathogenic species, for example Erwinia amylovora causes fireblight on crops. ...
Species X. albilineans X. ampelina X. arboricola X. axonopodis X. bromi X. campestris X. cassavae X. citri X. codiaei X. cucurbitae X. cynarae X. euvesicatoria X. frageriae X. gardneri X. hortorum X. hyacinthi X. melonis X. oryzae X. perforans X. phaseoli X. pisi X. populi X. sacchari X. theicola X...
Binomial name Escherichia coli T. Escherich, 1885 Escherichia coli (usually abbreviated to E. coli) is one of the main species of bacteria that live in the lower intestines of warm-blooded animals (including birds and mammals) and are necessary for the proper digestion of food. ...
Species S. boydii S. dysenteriae S. flexneri S. sonnei This article is about the bacteria. ...
Vibrio is a genus of bacteria, included in the gamma subgroup of the Proteobacteria. ...
Species S. aureus Staphylococcus (in Greek staphyle means bunch of grapes and coccos means granule) is a genus of gram-positive bacteria. ...
Species S. pneumoniae S. pyogenes S. viridans Streptococcus is a genus of spherical, Gram-positive bacteria of the phylum Firmicutes. ...
Benefits A clear benefit of phage therapy is that it does not have the potentially very severe adverse effects of antibiotics. Also it can be fast-acting, once the exact bacteria are identified and the phages administered. Another benefit of phage therapy is that although bacteria are able to develop resistance to phages the resistance is much easier to overcome. The reason behind this is that phages replicate and undergo natural selection and have probably been infecting bacteria since the beginning of life on this planet. Although bacteria evolve at a fast rate, so too will phages. Being smaller, they can mutate faster. Bacteria are most likely to modify the molecule that the phage targets, such as a cell surface glycoprotein, which is usually a bacterial receptor. In response to this modification, phages will evolve in such a way that counteracts this change, thus allowing them to continue targeting bacteria and causing cell lysis. As a consequence phage therapy is devoid of problems similar to antibiotic resistance. Phyla Actinobacteria Aquificae Chlamydiae Bacteroidetes/Chlorobi Chloroflexi Chrysiogenetes Cyanobacteria Deferribacteres Deinococcus-Thermus Dictyoglomi Fibrobacteres/Acidobacteria Firmicutes Fusobacteria Gemmatimonadetes Lentisphaerae Nitrospirae Planctomycetes Proteobacteria Spirochaetes Thermodesulfobacteria Thermomicrobia Thermotogae Verrucomicrobia Bacteria (singular: bacterium) are unicellular microorganisms. ...
For other uses, see Natural selection (disambiguation). ...
This article is about the tv programme Life on Earth. ...
This article is about biological evolution. ...
A glycoprotein is a macromolecule composed of a protein and a carbohydrate (an oligosaccharide). ...
This article is about the biological definition of the word Lysis. ...
Antibiotic resistance is the ability of a micro-organism to withstand the effects of an antibiotic. ...
Bacteriophages are often very specific, targeting only one or a few strains of bacteria. Traditional antibiotics usually have more wide-ranging effect, killing both harmful bacteria and useful bacteria such as those facilitating food digestion. The specificity of bacteriophages reduces the chance that useful bacteria are killed when fighting an infection.
Increasing evidence shows the ability of phages to travel to a required site — including the brain, where the blood brain barrier can be crossed — and multiply in the presence of an appropriate bacterial host, to combat infections such as meningitis. However the patient's immune system can, in some cases mount an immune response to the phage (2 out of 44 patients in a Polish trial [5]). The blood-brain barrier is a physical barrier between the blood vessels in the central nervous system, and the central nervous system itself. ...
Meningitis is the inflammation of the protective membranes covering the central nervous system, known collectively as the meninges. ...
Development and production is faster than antibiotics, on condition that the required recognition molecules are known. Staphylococcus aureus - Antibiotics test plate. ...
Research groups in the West are engineering a broader spectrum phage and also target MRSA treatments in a variety of forms - including impregnated wound dressings, preventative treatment for burn victims, phage-impregnated sutures. Enzobiotics are a new development at Rockefeller University that create enzymes from phage. These show potential for preventing secondary bacterial infections e.g. pneumonia developing with patients suffering from flu, otitis etc.. MRSA, or methicillin-resistant Staphylococcus aureus, is a bacterium that has developed antibiotic resistance, first to penicillin in 1947, and later to methicillin. ...
Application
Collection In its simplest form, phage treatment works by collecting local samples of water likely to contain high quantities of bacteria and bacteriophages, for example effluent outlets, sewage and other sources. They can also be extracted from corpses. The samples are taken and applied to the bacteria that are to be destroyed which have been cultured on growth medium. In the context of creating Plutonium at the Hanford Site, effluent refers to the cooling water that is discharged from a nuclear reactor that may or may not be radioactive. ...
Sewage is the mainly liquid waste containing some solids produced by humans which typically consists of washing water, faeces, urine, laundry waste and other material which goes down drains and toilets from households and industry. ...
The bacteria usually die, and the mixture is centrifuged. The phages collect on the top of the mixture and can be drawn off.
The phage solutions are then tested to see which ones show growth suppression effects (lysogeny) and/or destruction (lysis) of the target bacteria. The phage showing lysis are then amplified on cultures of the target bacteria, passed through a filter to remove all but the phages, then distributed.
Treatment Phages are "bacterium specific" and it is therefore necessary in many cases to take a swab from the patient and culture it prior to treatment. Occasionally, isolation of therapeutic phages can typically require a few months to complete, but clinics generally keep supplies of phage cocktails for the most common bacterial strains in a geographical area.
Phages in practice are applied orally, topically on infected wounds or spread onto surfaces, or used during surgical procedures. Injection is rarely used, avoiding any risks of trace chemical contaminants that may be present from the bacteria amplification stage,and recognizing that the immune system naturally fights against viruses introduced into the bloodstream or lymphatic system.
In August 2006, the United States Food and Drug Administration approved spraying meat with phages. Although this initially raised concerns since without mandatory labeling consumers won't be aware that meat and poultry products have been treated with the spray,[4] it confirms to the public that, for example, phages against Listeria are generally recognized as safe (GRAS status) within the worldwide scientific community and opens the way for other phages to also be recognized as having GRAS status. “FDA†redirects here. ...
Mandatory labelling of consumer products enables moral purchasing and avoidance of health problems like allergies. ...
Species Listeria monocytogenes Listeria ivanovii Listeria innocua Listeria welshimeri Listeria seegligeri Listeria grayi Listeria innocua Listeria is a bacterial genus containing six species. ...
Phage therapy is used for the treatment of a variety of bacterial infections including: laryngitis, skin infections, dysentery, conjunctivitis, periodontitis, gingivitis, sinusitis, urinary tract infections and intestinal infections, burns, boils, etc. - also poly-microbial biofilms on chronic wounds, ulcers and infected surgical sites. Laryngitis is an inflammation of the larynx. ...
Dysentery is the inflammation of the intestine causing severe diarrhea. ...
Periodontitis, formerly known as Pyorrhea, is the name of a collection of inflammatory diseases affecting the tissues that surround and support the teeth. ...
This article does not cite any references or sources. ...
Sinusitis is an inflammation of the paranasal sinuses, which may or may not be as a result of infection, from bacterial, fungal, viral, allergic or autoimmune issues. ...
A urinary tract infection (UTI) is a bacterial infection that affects any part of the urinary tract. ...
In 2007, Phase 2 clinical trials are nearing completion in a London throat, nose and ear hospital for Pseudomonas aeruginosa infections (otitis). Binomial name Pseudomonas aeruginosa (Schroeter 1872) Migula 1900 Synonyms Bacterium aeruginosum Schroeter 1872 Bacterium aeruginosum Cohn 1872 Micrococcus pyocyaneus Zopf 1884 Bacillus aeruginosus (Schroeter 1872) Trevisan 1885 Bacillus pyocyaneus (Zopf 1884) Flügge 1886 Pseudomonas pyocyanea (Zopf 1884) Migula 1895 Bacterium pyocyaneum (Zopf 1884) Lehmann and Neumann 1896 Pseudomonas polycolor...
Otitis is a general term for inflammation of the ear. ...
Phase 1 clinical trials are underway in the South West Regional Wound Care Center, Lubbock, Texas for an approved cocktail of phages, including P. aeruginosa, Staphylococcus aureus and Escherichia coli (better known as E. coli). Binomial name Rosenbach 1884 Staphylococcus aureus , (literally Golden Cluster Seed) the most common cause of staph infections, is a spherical bacterium, frequently living on the skin or in the nose of a person, that can cause a range of illnesses from minor skin infections (such as pimples, boils, and cellulitis...
E. coli redirects here. ...
Reviews of phage therapy indicate that more clinical and microbiological research is needed to meet current standards. [6]
Distribution Phages can usually be freeze dried and turned into pills without materially impacting efficacy. In pill form temperature stability up to 55C, and shelf lives of 14 months have been shown.
Other forms of administration can include application in liquid form. These vials are usually best kept refrigerated.
Oral administration works better when an antacid is included, as this increases the number of phages surviving passage through the stomach.
Topical administration often involves application to gauzes that are laid on the area to be treated.
Obstacles
General The host specificity of phage therapy may make it necessary for clinics to make different cocktails for treatment of the same infection or disease because the bacterial components of such diseases may differ from region to region or even person to person. Such a process would make it difficult for large scale production of phage therapy. Additionally, patent issues (specifically on living organisms) may complicate distribution for pharmaceutical companies wishing to have exclusive rights over their "invention"; making it unlikely that a for-profit corporation will invest capital in the widespread application of this technology.
In addition, due to the specificity of individual phages, for a high chance of success, a mixture of phages is often applied. This means that 'banks' containing many different phages are needed to be kept and regularly updated with new phages, which makes regulatory testing for safety harder and more expensive.
Some bacteria, for example clostridium and mycobacterium, have no known therapeutic phages available as yet. Species Clostridium acetobutylicum Clostridium aerotolerans Clostridium botulinum Clostridium colicanis Clostridium difficile Clostridium formicaceticum Clostridium novyi Clostridium perfringens Clostridium sordelli Clostridium tetani Clostridium piliforme Clostridium tyrobutyricum etc. ...
Species See text. ...
To work, the virus has to reach the site of the bacteria, and unlike antibiotics, viruses do not necessarily reach the same places that antibiotics can reach. [7]
Funding for phage therapy research and clinical trials is generally insufficient and difficult to obtain, since it is a lengthy and complex process to patent bacteriophage products. Scientists comment that 'the biggest hurdle is regulatory', whereas an official view is that individual phages would need proof individually because it would be too complicated to do as a combination, with many variables. CSLPublic awareness and education about phage therapy are generally limited to scientific or independent research rather than mainstream media. CSL can stand for: Chinese Super League, the premier league of football (soccer) in the Peoples Republic of China Commonwealth Serum Laboratories (1916-1961), Australian government agency; since privatised to form CSL Limited, an Australian biotechnology company Cosmopolitan Soccer League, a soccer league in the New York City area. ...
Safety Phage therapy is generally considered safe. As with antibiotic therapy and other methods of countering bacterial infections, endotoxins are released by the bacteria as they are destroyed within the patient (Herxheimer reaction).[8] This can cause symptoms of fever. Endotoxins are potentially toxic, natural compounds found inside pathogens such as bacteria. ...
Both Adolph Jarisch, an Australian dermatologist, and Karl Herxheimer, a German dermatologist, are credited with the discovery of the Herxheimer reaction. ...
Care has to be taken in manufacture that the phage medium is free of bacterial fragments and endotoxins from the production process.
Lysogenic bacteriophages are not generally used therapeutically. This group can act as a way for bacteria to exchange DNA, and this can help spread antibiotic resistance or even, theoretically, can make the bacteria pathogenic (see Cholera). It has been suggested that Lysogenic cycle be merged into this article or section. ...
Cholera (or Asiatic cholera or epidemic cholera) is a severe diarrheal disease caused by the bacterium Vibrio cholerae. ...
The lytic bacteriophages available for phage therapy are best kept refrigerated but discarded if the pale yellow clear liquid goes cloudy.
References
Notes - ^ Phage Therapy: Bacteriophages As Antibiotics, Evergreen, Access Date - 10/17/2007
- ^ [1]
- ^ Killer Cure, Phage International Inc.
- ^ a b Mc Grath S and van Sinderen D (editors). (2007). Bacteriophage: Genetics and Molecular Biology, 1st ed., Caister Academic Press. ISBN 978-1-904455-14-1 .
- ^ [2]
- ^ "Phage therapy: the Escherichia coli experience" by Harald Brüssow in Microbiology (2005) Volume 151, pages 2133-2140.
- ^ [3]
- ^ Evergreen PHAGE THERAPY: BACTERIOPHAGES AS ANTIBIOTICS
See also 14 March 2006--FDA trials?
Newspaper article on Phage
Bacteriophage
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