Phage+Therapy+to+Treat+Bacterial+Infections

=** Introduction **=

toc Phage therapy is a therapeutic method of using bacteriophages to help treat and prevent bacterial infections. There are many potential applications within the medical field including for those who are resistant to antibiotics.Bacteriophages or phages are bacterial viruses that tend to be host specific, meaning they infect only specific bacteria. Lytic phages multiply by lysing the bacterial cell to release newly formed phage particles [10]. The newly formed phages will then kill specific pathogenic bacterial strains.In comparison to antibiotics, phages are more specific and can be personalized to an individual’s bacterial infection [5]. Researchers are motivated in studying phage therapy because it can become an alternative method of treating bacterial infections and help the population that is antibiotic resistant.

=History=

Bacteriophages can be found anywhere. Bacteriophages came to light by Ernest Hanbury Hankin. He was a bacteriologist to the Government of the United Provinces and of the Central Provinces of India. He discovered that the waters from the Indian rivers Ganga and Yamuna contained a biological principle that destroyed cultures of cholera-inducing bacteria [12].

But in 1915 and 1917, Frederick Twort and Feliz d'Herelle were the first to isolate and use the bacteriophages [8]. However, D' Herelle was the first to independently use bacteriophages while studying patients suffering from bacillary dysentery [12]. His discovery introduced the use of bacteriophages in clinical medicine and attempt many different trials[8].

=** Studies Conducted **=

Studies and use of phage therapy are most prominent in Eastern Europe countries such as Russia, Georgia, and Poland [4][9]. The Eliava Institute of Bacteriophage in Tbilisi, Georgia, is dedicated to research of bacteriophages [4]. Phage therapy is not effective and mostly ignored in the West. It is a controversial topic in discussion. The main reason for why phage therapy isn't prominent within the West (specifically in the United States) is due to the lack of a framework and the lack of understanding the nature of bacteriophages [4][8]. Without the comprehensive knowledge and details of bacteriophage's function, scientists tend to ignore the potential usage of phage therapy.

** Experiments in Animal **
Extensive studies were conducted in various animals. In 1980, Smith and Huggins conducted a series of phage therapy in mice affected with //E. coli//. As a model, they use a K1 //E. coli// meningitis mouse. Low doses of phage were injected into the mouse and the results show the phage protected the mice against a massive dose of pathogen compared to multiple intramuscular injections of various antibiotics [1][4][11].

** Food Sanitation **
Phage therapy has not been completely ignored in the West. In 2006, the FDA announced the approval of the use of LMP-102 bacteriophage in use on Ready-to-Eat meat and poultry products. Six individual purified phages were used as an agent against //Listeria monocytogenes//, commonly found bacteria in contaminated food. It is resulted to be effective in killing over 170 strains of //Listeria//. The use of LMP-102 bacteriophage is now sprayed onto meat to prevent //Listeria// infection [4][6].

** Clinical Trial **
In France, a clinical trial will be launched called Phagoburn. Phagoburn is a biotechnological company specializing in research of bacteriophage. It is perhaps the largest study, evaluating phages as treatment [13]. The European Union (EU) is contributing 3.8 million euro (US$5.2 million) to the Phagoburn study [9]. The trial is in use for using phage therapy in serious burn victims. It is launched and conducted in 11 burn units in France, Switzerland, and Belgium. The trial will involve 220 patients total, and only 110 patients will either receive two bacteriophages: //Escherichia coli//, or //Pseudomonas aeruginosa// [2].

** Case Study **
The Eliava Institute of Bacteriophage in Tbilisi, Georgia conducted phage therapy on a 16-year-old boy with Netherton syndrome.Netherton syndrome (NS) is a rare genetic skin disorder that affects the immune system [7]. The boy was also antibiotic resistant and had chronic //Staphylococcus aureus// skin infection and allergy to multiple groups of antibiotics [14]. Two //Staphylococcus//-targeting phages were chosen in preparations, based on phage sensitivity testing-//Staphylococcus// bacteriophage, containing fully sequenced Sb1 phage, and //Pyobacteriophage// targeting //Staphylococcus spp., Streptococcus spp., E. coli, Pseudomonas aeruginosa, and Proteus spp// [14].The phage therapy was successful after a 6-month follow-up where his condition was stable, and his skin improved visually with the required hospitalization [14].

=** Conclusion **=

In evidence, phage therapy is a viable option for prevention and treating bacterial infection. Antibiotic resistance has become a global crisis, which alternative methods are needed to combat this threat, especially within Western medicine [3]. Eastern Europe has been using phage therapy successfully with positive results. There are many studies and trials created in studying specifically of bacteriophages. Institutions are set up in Georgia focusing on expanding phage therapy. It is clear that the ‘safe and controlled use of phage therapy will need detailed information on biological properties and behavior both in vitro and in vivo’ [11]. All dispositions against phage therapy need to be discarded and further research on the biological aspect and effects within the human immune system needs to be studied. For phage therapy to be completely FDA approved and to know detailed information about it can only be done through funding and interest to solve the global antibiotic threat.

= References =

[1] Brussow, H. (2005). Phage therapy: the Escherichia coli experience. Microbiology, 151(7), 2133-2140.

[2] Evaluation of phage therapy for the treatment of burn wound infections. (n.d.). Retrieved November 22, 2017

[3] Fauconnier, A. (2017). Regulating phage therapy. EMBO reports, 18(2), 198-200.

[4] Housby, J. N., & Mann, N. H. (2009). Phage therapy. Drug Discovery Today, 14(11-12), 536-540.

[5] Keen EC (2012) Phage therapy: concept to cure. Front. Microbio. 3:238

[6] Kutter, E. M., Kuhl, S. J., & Abedon, S. T. (2015). Re-establishing a place for phage therapy in western medicine. Future Microbiology, 10(5), 685-688.

[7] Netherton syndrome - Genetics Home Reference. (n.d.). Retrieved December 12, 2017, from https://ghr.nlm.nih.gov/condition/netherton-syndrome

[8] Nobrega, F. L., Costa, A. R., Kluskens, L. D., & Azeredo, J. (2015). Revisiting phage therapy: new applications for old resources. Trends in Microbiology, 23(4), 185-191.

[9] Reardon, S. (2014). Phage therapy gets revitalized. Nature, 510(7503), 15-16.

[10] Ryan, E. M., Gorman, S. P., Donnelly, R. F., & Gilmore, B. F. (2011). Recent advances in bacteriophage therapy: how delivery routes, formulation, concentration and timing influence the success of phage therapy. Journal of Pharmacy and Pharmacology, 63(10), 1253-1264.

[11] Skurnik, M., & Strauch, E. (2006). Phage therapy: Facts and fiction. International Journal of Medical Microbiology, 296(1), 5-14.

[12]Wittebole, X., Roock, S. D., & Opal, S. M. (2013). A historical overview of bacteriophage therapy as an alternative to antibiotics for the treatment of bacterial pathogens. //Virulence,5//(1), 226-235.

[13] Young, R., & Gill, J. J. (2015). Phage therapy redux--What is to be done? Science, 350(6265), 1163-1164.

[14] Zhvania, P., Hoyle, N. S., Nadareishvili, L., Nizharadze, D., & Kutateladze, M. (2017). Phage Therapy in a 16-Year-Old Boy with Netherton Syndrome. Frontiers in Medicine, 4.