[LUM#2] Viruses That Want to Help Us
It treats infections without the use of antibiotics. Long forgotten, phage therapy may well be making a comeback.
Millions of viruses
There are 1 million phages in every drop of seawater, 40 million in every gram of soil, and 100 million in our intestines. Bacteriophages are the most abundant microorganisms on our planet. “Their total number is estimated at10³¹,” note Oliver Kaltz and Michael Hochberg. “As small as they are, if we were to line them all up end to end, we would get a chain 100 million light-years long!” An inexhaustible resource.
They have saved millions of lives. They? Antibiotics: drugs that have revolutionized medicine since Alexander Fleming’s discovery of penicillin in 1928. But yesterday’s heroes have lost their luster. Today, they are under fire: their overuse over decades is responsible for the emergence of multidrug-resistant bacteria, against which they are now completely ineffective…
Resistance
This is a cause for concern for Michael Hochberg, a researcher at the Institute of Evolutionary Sciences in Montpellier:“It is now estimated that an antibiotic remains truly effective for only 5 to 10 years. During that time, very few new molecules are discovered.” How will we fight bacteria in the future? Perhaps with a weapon that’s been around for a long time: bacteriophages.“These natural enemies of bacteria attach themselves to the bacteria’s outer envelope, pierce their cell wall, and inject their genetic material. They then multiply inside their host, causing its death,” explains Oliver Kaltz, also a researcher at ISEM.
These “phages” enjoyed their heyday after their discovery by the French scientist Félix d’Hérelle in 1917. They are still used today in some Eastern European countries such as Georgia and Poland, but they fell into obscurity in Western countries after the 1940s. The reason? The rise of antibiotics, then considered the ultimate weapon against any bacterial infection.“Today, antibiotics have reached a dead end, which is sparking renewed interest in phage therapy,” the researchers explain.
Warning: Viruses
Whereas antibiotics attack bacteria indiscriminately—including the “good” bacteria that make up our gut flora—phages are much more selective: each virus generally targets a specific bacterium.“Phage therapy offers a tailored approach where antibiotic therapy is a one-size-fits-all solution,”explains Oliver Kaltz. This targeted therapy has another advantage: it limits the development of resistance. “Does a bacterium mutate and become resistant to the phage? The phage will also mutate to bypass the resistance. This is what we call a co-evolutionary process,” emphasize the ISEM researchers who are studying this co-evolutionary process in the laboratory and its potential significance for phage therapy.
Phage therapy could thus help combat bacteria that are resistant to multiple antibiotics, for which there are no longer any effective treatments.“Some French doctors have used phages to treat patients in desperate situations, and in some cases they have achieved spectacular results, ”explains Oliver Kaltz.
Could phages one day replace our good old antibiotics? For researchers, the answer is no:“The idea is rather to develop a therapy that combines bacteriophages and antibioticsto boost the treatment’s effectiveness.” This would also significantly reduce the use of these drugs and thus limit the development of antibiotic resistance.
Legal uncertainty
Government authorities are beginning to recognize the potential of phage therapy: in a 2012 report, the Center for Strategic Analysis, a French think tank and policy advisory body, proposed“clarifying the regulatory status of phage therapy and establishing a research program to assess its therapeutic potential.”
The path ahead for phage therapy, however, remains fraught with obstacles.“It isn’t taught in medical schools and remains unknown to most practitioners,” the researchers point out. And despite official recommendations, its regulatory status remains unclear.“Viruses are living organisms and aren’t simply well-defined active molecules. Under European law, they therefore do not have the same status as a chemical drug,” explains Oliver Kaltz. And so they do not generate the same enthusiasm from the pharmaceutical industry. “Especially since these living organisms cannot be patented,” adds Michael Hochberg.
Researchers lament that, in the absence of a clear regulatory framework, it remains difficult to obtain the necessary approvals to test the efficacy of phage therapy. However, this situation is beginning to improve with the launch of the first clinical trials (see box). The coming years will be decisive for the revival of this nearly forgotten—yet highly promising—therapy.
Phage therapy under trial
In 2013, Europe launched a clinical trial called Phagoburn. The goal: to test two phage cocktails against bacterial skin infections in patients with severe burns. The trial is being conducted at 11 burn centers in France, Switzerland, and Belgium. The French research project Phosa, launched in September 2015, aims to develop a phage mixture to combat the staphylococci responsible for osteoarticular infections. Veterinary medicine is also interested in the therapeutic potential of these viruses: in Germany, startups are developing phage cocktails for use against bacterial infections in livestock.
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