Phage therapy or viral fag therapy is the therapeutic use of bacteriophage to treat pathogenic bacterial infections. Phage therapy has many potential applications in human medicine as well as dentistry, veterinary science, and agriculture. If the target host for phage therapy is not an animal, the term "biocontrol" (as in the phag-producing bacterial biocontrol) is usually used, rather than "phage therapy."
Bacteriophages are much more specific than antibiotics. They are usually harmless not only for host organisms, but also for other beneficial bacteria, such as intestinal flora, reducing the likelihood of opportunistic infections. They have a high therapeutic index, ie phage therapy would be expected to cause some side effects. Because phages replicate in vivo (in living organism cells), smaller effective doses may be used. On the other hand, this specificity is also detrimental: the phage will only kill the bacteria if it matches the specific strain. Consequently, phage mixtures are often applied to increase the chances of success, or samples can be taken and the corresponding phage is identified and grown.
Phages tend to be more successful than antibiotics where there are biofilms covered by layers of polysaccharides, which are usually impenetrable to antibiotics. In the West, no therapy is currently allowed for use in humans, although the phage for killing the food poisoning bacteria ( Listeria ) is now in use.
Phages are currently being used therapeutically to treat bacterial infections that do not respond to conventional antibiotics, especially in Russia and Georgia. There is also a phage therapy unit in Wroclaw, Poland, established in 2005, the only center in the EU country.
Video Phage therapy
Histori
The discovery of bacteriophage was reported by Britain's Frederick Twort in 1915 and French-Canadian Felix d'HÃÆ'Â © relle in 1917. D'HÃÆ' Â © relle says that phage always appears in the stool of Shigella dysentric patients immediately before they begin to recover. He "quickly learned that bacteriophages were found in which bacteria proliferate: in ditches, in rivers that catch run-off waste from pipes, and in patients' stools heal". Phage therapy is immediately recognized by many as a key path forward for the eradication of pathogenic bacterial infections. A Georgian, George Eliava, is making a similar discovery. He traveled to the Pasteur Institute in Paris where he met d'HÃÆ' Â © relle, and in 1923 he founded the Eliava Institute in Tbilisi, Georgia, devoted to the development of phage therapy. Phage therapy is used in Russia, Georgia and Poland.
In Russia, extensive research and development soon begins in this field. In the United States during the commercialization of 1940 phage therapy performed by Eli Lilly and Company.
While knowledge is being gathered about the biology of phage and how to properly use phage cocktails, early use of phage therapy is often unreliable. When antibiotics were discovered in 1941 and marketed extensively in the US and Europe, Western scientists mostly lost interest in further use and studied phage therapy for some time.
Isolated from Western progress in antibiotic production in the 1940s, Russian scientists continue to develop phage therapy that has been successful in treating injured soldiers in field hospitals. During World War II, the Soviet Union used bacteriophage to treat many soldiers infected with various bacterial diseases, eg. dysentery and gangrene. Russian researchers continue to develop and perfect their care and publish their research and results. However, due to the scientific barriers of the Cold War, this knowledge is not translated and does not reproduce worldwide. A summary of this publication was published in English in 2009 in "A Literature Review of Practical Application of Bacteriophage Research".
There is an extensive library and research center at George Eliava Institute in Tbilisi, Georgia. Current phage therapy is a widespread form of treatment in the region.
As a result of the development of antibiotic resistance since 1950 and the advancement of scientific knowledge, there has been renewed worldwide interest in the ability of phage therapy to eradicate bacterial infections and chronic polymicrobial biofilms (including in industrial situations).
Phage has been investigated as a potential way to remove pathogens such as Campylobacter in raw foods and Listeria in fresh foods or to reduce bacteria from decaying foods. In agricultural practice, phage is used against pathogens such as Campylobacter, Escherichia and Salmonella in farm animals Lactococcus and < i> Vibrio pathogens in fish from aquaculture and Erwinia and Xanthomonas in crops that are important to agriculture. The oldest use is, however, in human medicine. Phages have been used to fight diarrheal diseases caused by E. coli , Shigella or Vibrio and against wound infections caused by facultative pathogens in the skin such as staphylococci and streptococci. More recently the phage therapy approach has been applied to systemic and even intracellular infections and the addition of non-replicated phag and isolated phag enzymes such as lysine to antimicrobial arsenic. However, clear evidence for the efficacy of phage approach in the field or hospital is not available.
Some interest in the West can be traced back to 1994, when Soothill pointed out (in animal models) that the use of phage can improve the success of skin grafts by reducing the underlying Pseudomonas aeruginosa infection. Recent studies have provided additional support for these findings in the model system.
Although not a "phage therapy" in the original sense, the use of phage as a delivery mechanism for traditional antibiotics is another possible therapeutic use. The use of phages to deliver antitumor agents has also been described in early in vitro experiments for cells in tissue culture.
In June 2015, the European Medicines Agency held a one-day workshop on therapeutic use of bacteriophage and in July 2015, the National Institutes of Health (USA) held a two-day workshop "Bacteriophage Therapy: Alternative Strategies to Combat Drug Resistance".
Maps Phage therapy
Potential benefits
Treatment of bacteriophages offers a possible alternative to the treatment of conventional antibiotics for bacterial infections. It is conceivable that, although bacteria can develop resistance to phages, resistance may be easier to overcome than resistance to antibiotics. Just as bacteria can evolve, viruses can evolve to overcome resistance.
Bacteriophages are very specific, targeting only one or several strains of bacteria. Traditional antibiotics have a wider effect, killing harmful bacteria and beneficial bacteria such as those that facilitate the digestion of food. Species and specificity of bacteriophage strains make it unlikely that harmless or useful bacteria will be killed when fighting infection.
Some evidence suggests the phage ability to travel to the site as needed - including the brain, where the cerebral blood barrier can be crossed - and breed in the presence of the host of the right bacteria, to fight infections such as meningitis.
Some research groups in the West are broader phage spectrum engineering, as well as various forms of MRSA treatment, including implanted wound dressings, preventive care for burn victims, phag-implanted sutures. Enzybiotics is a new development at Rockefeller University that creates enzymes from phage. Pure recombinant phage enzymes can be used as separate antibacterial agents in their own right.
Phage therapy also has the potential to prevent or treat coral infections. This can help decrease corals worldwide.
Apps
Collection
The simplest method of phage treatment involves the collection of local water samples that may contain large amounts of bacteria and bacteriophages, such as outlet, sewage, and other sources. Samples were taken and applied to the bacteria to be destroyed which had been cultured on the growth medium.
If the bacteria die, as is usually the case, the mixture is centrifuged; The phages collect at the top of the mixture and can be drawn.
The phage solution was then tested to see which showed the effect of growth suppression (lysogeny) or the destruction (lysis) of the target bacteria. The phag indicating the lysis is then amplified on the bacterial culture of the target, passing the filter to remove all phage, then distributed.
Treatment
Phages are "bacteria-specific" and therefore are necessary in many cases to take samples from patients and cultivate them before treatment. Sometimes, therapeutic phage isolation requires several months to complete, but clinics generally store phage cocktail supplies for the most common bacterial strains in the geographic region.
The phases in practice are applied orally, topically on the wound infected or spread to the surface, or used during the surgical procedure. Injection is rarely used, avoiding the risk of chemical contaminants that may arise from the stage of bacterial amplification, and recognizing that the immune system naturally fights viruses infused into the bloodstream or lymphatic system.
In 2007, a 1/2 phase clinical trial was completed at Royal National Throat, Ear and Nose Hospital, London, for Pseudomonas aeruginosa infection (otitis). The Phase-1/Phase-2 study documentation was published in August 2009 in the journal Clinical Otolaryngology.
Phase 1 clinical trials have now been completed at Southwest Regional Lung Treatment Center, Lubbock, Texas for phag-approved cocktails against bacteria, including P. aeruginosa , Staphylococcus aureus and Escherichia coli (better known as E. coli ). Cocktail fags for clinical trials are developed and supplied by Intralytix.
Phage therapy reviews indicate that clinical and microbiological research is needed to meet current standards.
Administration
Phages can usually be frozen and converted into pills without reducing material efficiency. Temperature stability up to 55Ã, Â ° C and 14 months' shelf life have been shown for some types of phage in pill form.
Application in liquid form is possible, stored preferably in a cooled bottle.
Oral administration works better when antacids are introduced, as this increases the amount of phag surviving through the stomach.
Topical administration often involves applications for screening placed in the area to be treated.
Phage IV drip therapy was successfully used to treat patients with MDR Acinetobacter baumannii at Thornton Hospital at UC San Diego.
Obstacle
The high specificity of bacterial strains from phage therapy may make it necessary for the clinic to make different cocktails for the treatment of the same infection or disease because the bacterial component of the disease may vary from region to region or even from person to person. In addition, this means that 'banks' contain many different phages should be maintained and updated regularly with new phage.
Further, bacteria can evolve different receptors either before or during treatment; this can prevent the phage from completely eradicating bacteria.
The need for phage banks makes regulatory testing for security harder and more costly under current rules in most countries. Such a process would complicate the use of phage therapy on a large scale. In addition, patent issues (especially in living organisms) can complicate the distribution for pharmaceutical companies that want to have exclusive rights to their "discovery", which would prevent commercial firms from investing capital in this regard.
As has been known for at least thirty years, mycobacteria such as Mycobacterium tuberculosis have specific bacteriophages. No lithic phagsi has been found for Clostridium difficile , which is responsible for many nosocomial diseases, but some phages being (integrated in the genome, also called lysogenic) are known for this species ; this opens up a joyous path but with the added risk as discussed below.
To work, the virus must reach the bacterial site, and the virus can sometimes reach places that can not be reached by antibiotics. For example, jazz bassist Alfred Gertler has a bacterial infection in his bones after an ankle fracture. A doctor in the US told him that the legs had to be amputated. She refused and was mostly slept for four years until phage therapy at the Eliava Institute in Tbilisi, Georgia, eliminated bacterial infections. Then he underwent surgery to repair his ankle and continued his career and family life.
Funding for phage therapy research and clinical trials is generally insufficient and difficult to obtain, as this is a long and complicated process for patenting bacteriophage products. Scientists commented that 'the biggest hurdle is regulation', whereas the official view is that individual phage will need evidence individually because it would be too complicated to do as a combination, with many variables. Due to the specificity of the phage, phage therapy will be most effective with cocktail injections, which are generally rejected by the US Food and Drug Administration (FDA). Researchers and observers estimate that for successful phage therapy, the FDA should change its regulatory stance on drug cocktail combinations. Public awareness and education about phage therapy is generally limited to scientific or independent research rather than mainstream media.
Negative public perception of the virus can also play a role in the reluctance to use phage therapy.
Legislation
Approval of phage therapy for use in humans has not been provided in Western countries with some exceptions. In the United States, the laws of Washington and Oregon allow naturopathic doctors to use legally experimental therapy in the world experimentally, and in Texas fags are considered natural substances and can be used in addition (but not as a substitute for) traditional therapies (they have been used routinely at the wound care clinic in Lubbock, TX, since 2006).
In 2013, the conference "Twenty-two annual Annual International Anniversary of Evergreen... attracted 170 participants from 35 countries, including corporate leaders and institutes involved with human phage therapy from France, Australia, Georgia, Poland and the United States. "
Security
Many difficulties in obtaining regulatory approval have proven to be a risk of using self-replicating entities that have the ability to evolve.
Like antibiotic therapy and other methods to fight bacterial infections, endotoxins are released by bacteria because they are destroyed in the patient (Herxheimer's reaction). This can cause symptoms of fever; in extreme cases, toxic shock (a problem also seen with antibiotics) is possible. Janakiraman Ramachandran argues that this complication can be avoided in the type of infection in which this reaction may occur by using gene-engineered bacteriophages that have their genes responsible for producing endolysin removed. Without this gene, the host bacteria is still dead but remains intact because the lysis is disabled. On the other hand, this modification halts the exponential growth of phage, so that a given phage means a single bacterial cell dies. Eventually these dead cells are consumed by the normal housekeeping task of phagocytes, which utilize enzymes to break down all the bacteria and their contents into proteins, harmless polysaccharides and lipids.
Medium (or lysogenic) bacteriophages are not generally used therapeutically, as this group may act as a way for bacteria to exchange DNA; this may help spread antibiotic resistance or even, theoretically, create pathogenic bacteria (see Cholera). Carl Merrill claims that a harmless corynebacterium strain may have been converted into C. diphtheriae <"which probably killed one third of all Europeans who came to North America in the seventeenth century. Fortunately, many phags seem lytic with only a slight likelihood of being lysogenic.
Benefits
In Russia, the preparation of a mixed phage can have a therapeutic efficacy of 50%. This is equivalent to a complete cure of 50 of 100 patients with antibiotic-resistant infections. A rate of only 50% is likely due to individual choice in mixing and ineffective diagnosis of infectious agents.
Other animals
Brigham Young University is currently researching the use of phage therapy to treat American foulbrood on honeybees. Phage therapy is also being investigated for potential applications in cultivation.
Cultural impact
The 1925 novel and 1926 Pulitzer prize winner Arrowsmith uses phag therapy as a plot point.
Novel 2002 Greg Bear Vital featuring phage therapy, based on Soviet research, is used to transfer genetic material.
A collection of military history essays of 2012 on the changing role of women in warfare, "Women in War - from front of house to front line" includes chapters featuring phage therapy: "Chapter 17: Women who melted the Cold War."
See also
- Antimicrobial Resistance
- Lysin
- Enzybiotics
- Phage monograph
- Phage screen
- Phagoburn
Note
References
External links
- iBiologi Video: Phage Therapy (2016)
- Elkadi, Omar Anwar (2014). "Phage Therapy: A new old antibacterial therapy". El Mednifico Journal . 2 (3): 311. doi: 10.18035/emj.v2i3.202.
- Popular Science: The Next Phage (2009)
- Thiel, Karl (2004). "Old dogma, new trick - 21th Century fag therapy". Natural Biotechnology . 22 (1): 31-6. doi: 10.1038/nbt0104-31. PMID 14704699. Source of the article : Wikipedia
0 Comments