What type of phage specifically kills bacteria
The treatment worked. But broad-based clinical trials are still needed before any phage therapies can be approved. Materials provided by ETH Zurich. Note: Content may be edited for style and length. Science News. Genetically modified phages Under the direction of Samuel Kilcher, an "Ambizione" fellow funded by the Swiss National Science Foundation, researchers from the Institute of Food, Nutrition and Health IFNH at ETH Zurich have genetically reprogrammed phages to produce synthetic phages that recognize and attack a broader range of bacterial strains beyond their natural host.
Loessner, Samuel Kilcher. Cell Reports , ; 29 5 : DOI: ScienceDaily, 4 November ETH Zurich. Synthetic phages with programmable specificity.
Retrieved November 10, from www. This has been suggested to provide an extra level of immunity against bacterial infections. New research shows that bacteriophages viruses that infect bacteria can contribute to new functions by revealing hidden potential ScienceDaily shares links with sites in the TrendMD network and earns revenue from third-party advertisers, where indicated.
Print Email Share. Bacteria also replicate quickly and the selective pressure of antibiotics encourages the emergence of antibiotic-resistant strains. In contrast, phages are very specific about the bacteria they infect, so the collateral damage to other bacteria or human cells is minimal. Though bacteria can develop resistance to phage they can eventually shed the surface receptors that phages use to dock and enter the cells , the risk is low.
Such an approach can be expedited with the use of phage libraries. Decades of anecdotal reports from Russia, Poland and the Republic of Georgia, as well as preclinical studies in animals, indicate that phage therapy is likely safe for most people, at least when applied topically to the skin. Septic shock is the main worry for doctors considering phage therapy. Yet this is also a concern for some currently available antibiotics. Finally, phages are able to transfer DNA from one bacterium to another, in a naturally and commonly occurring process known as transduction.
Phage manipulation and engineered introduction could theoretically introduce new virulence factors or toxins to already pathogenic bacteria, or convert non-pathogenic bacteria into pathogens. However, this issue can be overcome by pre-selecting phages that have been carefully screened for toxins and virulence factors — an effort that can be facilitated by using ever-expanding phage libraries that several teams are currently developing around the world.
The main challenges to phage therapy are 1 doctors need to know exactly which bacterial strain is causing the infection and 2 they must have several phages that specifically target that strain readily available, ideally from a large phage library that can be screened for a suitable phage cocktail that matches the bacteria.
Compounding the latter problem, most pharmaceutical companies are reluctant to dedicate resources to phage therapy development and commercialization. Lack of regulatory approval for phage therapy is also an issue. Regulatory agencies such as the US Food and Drug Administration FDA currently lack streamlined review and approval mechanisms to accommodate personalization and flexibility on a large scale.
Diagnostic innovations that take advantage of genomic sequencing and mass spectrometry may soon meet the need for rapid and accurate bacterial identification.
Navy Medical Research Center and other teams around the world, who are currently building phage libraries. Looking further ahead, other technology advances may help make phage therapy even more specific and help with the patent problem.
Companies then might be more likely to obtain patents on unique phage or phage cocktails, making them a commercially viable investment. We urgently need an alternative method to fight bacterial infection. One promising method for killing bacteria is to use bacteriophages: viruses that infect and kill bacteria.
In the following years, phages were employed to treat dysentery and cholera with success. These phages were isolated from the stool of patients who unexpectedly recovered from the illness. Scientists speculated that there was something in these lucky patients that helped to remove harmful bacteria from their guts.
They isolated phages from the stools, purified them, and gave the phages to other patients. Despite the early success, phages therapy was eclipsed by the discovery of penicillin and the rise of antibiotics. At the time phages were initially used for treatment of cholera, scientists had only just begun to study viruses and speculate about how phages work.
It was not until that the first images of phages were obtained using an electron microscope. We now know that phages are viruses that infect only bacteria. As a type of virus , phages cannot live and reproduce alone. In general , phages start their killing first by recognizing and landing on a bacteria. Each type of phages has a specific landing pad. The phage then injects its DNA into the bacteria. Lastly, the phage produces toxic chemicals that rupture the bacterial host from inside out, releasing its newly made children to the outside to infect even more bacteria Figure 1.
An antibiotic is a chemical that kills bacteria. It does so by disrupting one or more of the important processes that bacteria need to survive. While antibiotics have revolutionized medicine and are often very effective in stopping bacterial infection, well-developed phages could have several advantages over antibiotics.
First, phages are specific to one species of bacteria and are therefore unlikely to disturb beneficial microbe living in our guts. The human body is populated by over a thousand species of microbes, which are estimated to make up about pounds of our total body weight. These microbes do important jobs for us, such as helping us make nutrients we cannot make ourselves.
Because many antibiotics kill bacteria indiscriminately, treating an infection with an antibiotic results also in killing this beneficial gut bacteria. Each phage, on the other hand, evolved to kill just a specific set of bacteria. Because phage kills with a narrow scope, it could be used to cure an infection without disturbing the community of beneficial bacteria in our body.
Second, phages are able to kill antibiotic-resistant bacteria. The way that phages kill bacteria is harder for bacteria to develop resistance against compared to the way that antibiotics kill bacteria. In addition, many bacteria develop biofilm — a thick layer of viscous materials that protect them from antibiotics.
Many phages are equipped with tools that can digest this biofilm. With the exception of treatment options available in a few countries, phages have been largely abandoned as a treatment for bacterial infection. One main reason is because antibiotics have been working well enough over the past 50 years that most countries have not re-initiated a study on the clinical uses of phages.
But another reason is that there are some limitations for using phages as a treatment. First, phages are more difficult to prepare cleanly. To produce phages, first scientists have to grow a large quantity of bacteria that is the natural host of the phage. The bacteria is then infected with the phages, and the phages in turn reproduce and kill all the bacteria. The difficulty begins with the isolation of live phages from a multitude of dead bacteria corpses. If not removed from the final medication given to the patient, dead bacteria bodies could trigger a deadly immune response called sepsis.
If the concentration is too low, phage therapy would inefficacious. Many of the early commercial phage products were of poor quality and incapable of treating infectious disease, leading to phage therapy being discredited. Second, phage takes a longer time to employ in a treatment compared to antibiotics. Because a single type of phage can only infect a few species of bacteria, phage selection has to be done with care.
First, doctors have to figure out the identity of bacteria that is causing the illness. Then they have to check whether the available phages could kill this strain of bacteria.
If not, they have to search for new phages that could do the job. This process takes time that the patients may not have — especially when phages are used only as a last resort on very ill patients. On the other hand, because antibiotics kill indiscriminately, doctors can prescribe an antibiotic to treat a patient without needing to first identify the specific type of bacteria.
Other concerns about phage therapy are centered on its safety and efficacy. Because the western world abandoned phage therapy many decades ago, there is little data about these topics available.
However, research on phage therapy continues and prospers in France and eastern European countries, especially in Georgia. From their studies , phage therapy does not exhibit any major safety concerns. Now that more and more bacteria have developed resistance to antibiotics, scientists around the world have a renewed interests in phages. The European Union invested 5 millions euros in Phagoburn , a project that studies the use of phages to prevent skin infections in burn victims Figure 2.
In the USA, the FDA approved ListshieldTM , a food additive containing phages, that kills Listeria monocytogenes, one of the most virulent foodborne pathogens and one cause of meningitis.
Currently, many clinical trials using phage to treat or prevent bacterial infections such tuberculosis and MRSA are undergoing. Despite the fact that phage therapy is not yet approved by FDA, phages have already been used to save lives in experimental treatments. A miraculous recovery of a patient who suffered from antibiotic-resistant bacteria was reported in San Diego.
While on a vacation in Egypt, Tom Patterson was infected by a multidrug-resistant strain of Acinetobacter baumannii. He was flown back to California and treated with antibiotics for over days, but Patterson did not get better and fell into coma. He was finally saved by a cocktail of phages purified from sewage in Texas. In the near future, as antibiotics lose their effectiveness, we may begin to hear more stories like this.
And one day, phage might move from our last resort against antibiotic-resistant bacteria to our first line of defense. Thanks for this perfect text. I am Ph. D student in bacteriology and my thesis is about phage therapy in burn wound infections.
I really interested in phage therapy and I hope to do my best in my own thesis. A very successful laboratory in the eastern block had isolated phages that were able to treat almost all bacterial infections. When the eastern block dismantled, the laboratory opened all its secrets in the hope that the research could continue.
However no one was interested primaraly because the Drugs companies could not make any money out of it. It is scandalous that many have died, who could have been succesfully treated with phages, because because of the Wests money orientated drugs culture.
For those who have untreatable bacterial infections , many can be treated by the instute in Georgia where research continues, Why can they not be treated here in the UK?
A lot of research is needed in order to ensure the safety of phage treatments. I agree with you that research on phages should be sped up.
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