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Phage therapy: A novel therapeutic strategy for chronic diseases

Xuejun Sun | Dec 3, 2014 | 23,053 views
Can the high host specificity of phages be used to our advantage, in order to establish a preventive and therapeutic method for some chronic diseases?

An interdisciplinary approach is usually an effective way to generate innovative research ideas. As an example for the readers, I will present an idea that was developed as part of a literature review.

Studies have confirmed the effectiveness of using phages to treat drug-resistant bacterial infections. The existence of pathogenic bacterial species in the intestine can have several unfavorable outcomes, including obesity-related diabetes. However, one question remains: Can the high host specificity of phages be used to our advantage, in order to establish a preventive and therapeutic method for some chronic diseases?

The human body harbors trillions of bacteria and other microorganisms. These microorganisms are present on the skin as well as in the intestinal canal, mouth, and other parts of body. Microorganisms usually found at any anatomical site are referred to as the normal flora, and sometimes, as the “indigenous microbiota.” Flora genomics is a field that involves studies on the normal flora. Many of these bacteria, especially those residing in the intestines, play an important role in maintaining human health.

Few years ago, scientists based in the USA examined these bacterial species as part of the Human Microbiome Project. Their research revealed that more than 10,000 different bacterial species reside in a healthy human adult. Some studies have shown that certain pathogenic intestinal bacteria can promote obesity-induced diabetes and other diseases. Suppressing the growth of these bacteria can improve health and even cure certain diseases. The use of specific antibiotics is the simplest approach to kill these bacteria; however, a major disadvantage of antibiotic use is poor selectivity and disturbance to the beneficial intestinal flora. Therefore, it is not a suitable method to treat chronic diseases. Hence, more specific anti-bacterial methods are required for the prevention and treatment of such diseases.

The Cold War had made it difficult for patients in the former Soviet Union to access the advanced range of antibiotics developed by the western countries. To overcome this bottleneck, the former Soviet Union heavily funded groups working toward the development of suitable viral (bacteriophage) therapies to combat bacterial infections. Phagotherapy or bacteriophage therapy is still quite popular in Russia, Georgia, and Poland; however, other countries have not adopted this approach.

With the alarming rise in antibiotic resistance, scientists and governments of the European countries and the USA have started to ponder over phagotherapy as an alternative treatment strategy to deal with bacterial drug resistance. In March 2014, the National Institute of Allergy and Infectious Diseases (NIH, USA) listed phagotherapy as one of the seven methods to deal with antibiotic resistance.

At the American Society for Microbiology Conference held in Boston in May 2014, Professor Grégory Resch from the University of Lausanne, Switzerland, introduced Phagoburn, the first multicenter clinical research project launched in Europe involving phagotherapy. The research project, an initiative by the European Union, aims to develop methods using phages to treat human infections.

The primary advantage of this approach is its host specificity; a certain type of phage invades and kills only a certain bacterial species. Accuracy is required to target certain harmful bacteria in the normal flora, which can be achieved using phages because of their unique ability to infect specific host bacterial species. Years of research have allowed scientists to realize that it is relatively simple to identify phages and their corresponding host bacteria. The natural environment is the largest resource for phages, and cross-infectivity is very rare. Theoretically, almost each bacterial species is infected by one or more corresponding phage.

In addition, advancements in genetic engineering have made it possible to construct artificial phages that can specifically infect target bacteria. Recently, synthetic biologist Timothy Lu and his team working at the Massachusetts Institute of Technology constructed an engineered phage by using a DNA-programming technique (clustered regularly interspaced short palindromic repeats; CRISPR) that can specifically infect and kill drug-resistant bacteria. This phage invades the target bacterium carrying genes for drug resistance, along with its RNA fragments. If the bacterium carries the genes for drug resistance, these RNA fragments will be able to bind to such sequences. This, in turn, will allow the Cas9 enzyme to cleave the bacterium's DNA, thus, killing the bacterium. In future, more such artificial phages can be constructed using this strategy.

In conclusion, the host specificity of both natural and artificial phages can be effectively used to attack specific bacteria. This will help to establish a suitable preventive method and to effectively treat chronic diseases by adjusting the intestinal flora. Appropriate animal experiments need to be designed to verify the effects and specificity of this method. Human trials can be undertaken to check for effectiveness only after confirming the long-term safety of this therapeutic method. The only risks associated with this approach are a possible disturbance to the intestinal flora and failure to achieve the goal of disease prevention and treatment.

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