Image by Proceedings of the National Academy of Sciences (PNAS)
iGEM Project 2023 | Part 5
At the beginning of this series, we mentioned that phages immediately aroused great interest in the treatment of bacterial infections; these microorganisms were indeed discovered a few years earlier than antibiotics. Subsequently, however, when the “revolution” of antibiotics began in 1928, as we have already explained, phages and their use in therapy fell into oblivion. In fact, antibiotics are simple molecules, easy to synthesize and produce on a large scale, transportable and dispensable in a simple way; in short, they are almost perfect drugs. Thanks to their fast diffusion, as we have seen, their large use becomes an abuse quickly, they are being used for everything and badly, without completing the therapy cycles, and sometimes also for non-bacterial infections. This phenomenon quickly brought serious consequences: bacteria become resistant, a selection process is set up against the strains that have developed the ability to live in the presence of the antibiotic, so much that they become prevalent in the environment. Therefore, more and more active principles become useless, completely ineffective, and a struggle begins, which continues today: an endless race for the newest molecule, a spasmodic and economically excruciating search for ever new drugs that can be active against these “super- bugs”.
When the possibilities start to run out, and the news is hard to arrive, we look to the past, a metaphor to say how phage therapies are coming back. Unfortunately, they are not yet protagonists of clinical practice, but remain relegated to those few cases where hope seems lost. If we scroll through the news headlines and scientific publications, we come across titles such as “patient affected by a multi-resistant infection treated with a virus” more and more frequently. Up to now, they represent an extraordinary event, but things are likely to change in a short time.
Why are these phages so useful, and why might they be our “last resource”? So far, we have not mentioned one feature of these organisms – tropism. Tropism is defined as the “ability of a microorganism to orient itself towards a specific organ, tissue or cell”. In other words it means that a phage is capable of infecting only specific cells belonging to a given species or subspecies. As a consequence, this causes the extreme specificity of the infection; a phage only infects a certain bacterium if appropriate structures are recognized. This specificity is an extraordinary characteristic for us, because the big problem of antibiotics is exactly the damage they induce towards all bacteria present in our body, even the good ones essential for our health – think of the intestinal flora (for this reason, together with the pill, the doctor often also recommends lactic ferments). A therapy based on these viruses would have the ability to be directed exclusively against the pathogen we want to eliminate, without interfering with the normal microbiome (the set of bacterial populations naturally present in our body), and there are many studies supporting this.
To date, there are several examples where phage cocktails, such as those we mentioned beofre, have been used as compassionate therapies for patients with multi-resistant infections. As can be imagined, it is not yet a standardized and common therapy, although in some cases it has been effective in curing the disease. We are still facing several challenges as the tropism raises many problems. It is necessary to find the right phage for the desired bacteria, and it is not always easy. Moreover, physically finding new viruses requires a considerable effort of analysis, so much that samples are being taken from everywhere, with promising results.
Giving a conclusion to such an evolving topic is quite complex so I will limit myself to a few comments. As we have seen, phages have the potential to be therapeutic tools of great interest. I used the word “tools” to stress that bacteriophages probably will not have a great future in medicine as they are, but rather as vehicles for a more complex therapeutic system. Up to now, we just have to wait and see what man will do with the most lethal organism on Earth.