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Bacteriophages – our knights in shining armour?
Since the discovery of penicillin in the early 20th century the image of bacterial infections has changed dramatically. Numerous diseases that have been a death warrant before do no longer pose a thread to modern medicine. But, soon after Fleming’s famous discovery a resistant strain of Staphylococcus was found that urged the need for new antibiotics. And thus, up to date, a plethora of different antibiotics have been developed. However, 100 years after the discovery of penicillin, the world is now facing another bacterial threat, this time caused by the cure itself. In their global report on surveillance, the WHO alerts that without urgent action we are heading for a post-antibiotic era, in which common infections and minor injuries can once again kill. This crisis is not only attributed to the overuse and misuse of antibiotics, but also to the lack of new innovative drugs.
Using natural predators
One alternative to antibiotics may be the use of bacteriophages, viruses that use bacteria as their host organism for replication processes, thus leading to the bacteria’s death. Felix d’Herelle, a microbiologist, was one of the first persons observing these parasitizing effects of the virus. Soon after the official discovery of bacteriophages d’Herelle and others were able to use them therapeutically: It was shown that bacterial infections could be treated with specific (bacterio-)phage preparations that were either digested or locally applied on the open wounds.
The upside of being picky
The advantage of phages lies in their strong specifity. In order to replicate within a bacterium phages need to make highly specific contact with particular bacterial surface features. Therefore, phages can be used for a more targeted accurate attack on pathogenic bacteria without affecting the beneficial microbes that live within our body. Moreover, bacteriophages are inherently harmless to humans.
After the initial contact between the phage and its target, its DNA is injected into the bacterial host. Afterwards the replication process of the phage DNA starts and ultimately leads to the release of the newly generated mature phages. Besides using bacteria as hosts for the generation of new phages, these viruses can also genetically modify bacteria by integrating their own DNA into the bacterial chromosome. Due to this ability phages have been used extensively in genetic engineering for decades. The highly specific antibacterial properties of phages however, as described by d’Herelle, have fallen into oblivion with the rising success of antibiotics in the mid 20th century.
Catching up with the East
But, as a consequence of the cold war, the East did not benefit from this scientific development. Hence, their research continued to focus on the use of bacteriophages. Unsurprisingly, the leading institute on phage research, the Eliava institute, is located in Tbilissi, Georgia. In recent years this alternative approach is taken more and more seriously in the “West” as well: Phagoburn, an EU-funded multi-centered clinical trial of phage therapy for human infections, is the first large scale trial evaluating the safety, effectiveness and pharmacodynamics of phage therapy for burn victims who may be at risk for antibiotic-resistant bacteria. The project aims to contribute to the optimization of current regulatory guidelines on phage therapy. Phage researchers all around the world hope that this project will lay groundwork for future approaches. Moreover, the concept of classic phage therapy was already taken one step ahead by MIT scientist Dr. Lu. His lab considered using genetically engineered phages for future therapy to kill antibiotic-resistant bacteria even more efficiently. Experiments in waxworm larvae were quite promising, so that researchers started to test these phages in mice.
But, despite all of these promising results it must to be taken in mind that unlike synthetically produced antibiotics, bacteriophages are biological entities with the capability to adopt and evolve and thus a lot of research is still needed.
Widuri Kho
Medical Advising at antwerpes
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References
- Reardon S. Nature 2014;510:15-16.
- Alavidze Z et al. Biotechnol J 2016;11:1-6.
- Young R, and J J Gill. Science 2015;350:1163-1164.
- Sulakvelidze A et al. Antimicrob Agents Chemother 2001;45:649-659.
