It is doubtful whether viruses are living beings, but there is certainty about their role in terrestrial life. These tiny entities, which make a microscopic bacteria seem enormous, seem very simple: a piece of genetic material encapsulated in protein that hijacks the cells of other living beings to put them at the service of its reproduction. It is estimated that sea viruses kill 20% of microbes of the ocean every day and that renew all the phytoplankton on the planet in a week. In this process of cell destruction and renewal, according to an article published in Science Advancesare released into all the oceans around 140 gigatons of carbon per year, almost four times more than burning fossil fuels.
These life regulators also play a similar role in the human organism. In each of us there are more than 10,000 species of bacteria, a balanced ecosystem that keeps us healthy and that viruses preserve. Although bacteriophages were used a century ago to combat bacterial infections such as bubonic plague or cholera, the success of antibiotics from the 1930s relegated the viral solution to contagious diseases in almost the entire world, maintaining its prestige, mainly, in the Soviet Union. In recent years, the increase in bacterial resistance has brought back interest in phages, which have already saved terminally ill patients.
The rebirth of viruses bacteria killer It has meant that the potential of these beings as regulators of human health is also valued. In an article he publishes today Magazine Science, a group of researchers from the laboratory of They were Elinav, at the Weizmann Institute (Revohot, Israel), raise the possibilities of phages to treat non-infectious diseases. Cancer, obesity, diabetes or neurological disorders are influenced by imbalances in the population of bacteria that inhabit us, and phages can be a tool to restore order. Elinav and his team have already done A study in which they proved that an orally administered phage therapy to treat mice with irritable bowel was able to control a strain of the bacteria in mice Klebsiella pneumoniae and alleviate the symptoms of the disease.
Stool transplants, as a way to combat obesity or depression, achieve their effect by bringing the sick person into the balanced bacterial ecosystem of a healthy person. Pilar Domingo-Calap, researcher at the Institute for Integrative Systems Biology (University of Valencia-CSIC), explains that “there are studies that show that, in this type of transplants, it is the viral part that modifies the bacterial communities.” “Now, we have to study how to use these viruses as probiotics to improve the bacterial population of the intestine,” she adds.
Among the advantages of these treatments, the Elinav team highlights that each type of virus is a specific enemy of a type of bacteria. Once selected, the phages only attack the population of bacteria that is generating the imbalance, “minimizing damage to the surrounding microbiota.” This way of working is different from that of antibiotic treatments, which kill harmful bacteria, but also wreak havoc on the good ones, which are the majority and not only do they not cause harm, but are necessary. Furthermore, once it has entered the body and begins to attack bacteria, every time it enters one of them, it reproduces and makes it explode, releasing new phages that continue with the task.
Phages, which lost their battle against antibiotics when medical solutions were intended for large population groups, make sense in a world that seeks personalized medicine. Treatment with these viruses must be designed for each individual, culturing bacteria from the patient along with potential phages to choose those with specific antibacterial capacity. “Metagenomic profiles could be used as a complementary diagnosis to identify [las bacterias] that contribute the most to the disease in the patient,” point out the authors of the article Science. Next, it is necessary to isolate the phages that may be most useful from the environment. To optimize the process, phage biobanks would be useful, characterized to know their effects, against which bacteria they can work or what adverse effects they can present.
As in other fields of medicine, when phages against a specific bacteria are not found in nature, synthetic biology could be used to modify natural viruses and direct them against a specific target. This would also make it possible to introduce changes to adapt to the mutations of the bacteria caused by the treatments. The CRISPR system, now known for its use in gene editing, is one of the methods used by bacteria to learn from their contacts with viruses and repel them. However, Domingo-Calap points out that “CRISPR is only one of the systems that bacteria have to block the entry of phages, and phages also have anti-CRISPR systems, they evolve and adapt.”
In this initial development phase, in addition to more basic research and the launch of more clinical trials in humans, Elinav’s group highlights the need for special regulation. “As phages are live biological agents, they present numerous differences from traditional medicines and therefore deserve particular regulatory consideration,” they write. For example, when drug combinations are approved, as is the case in cancer treatments, evidence is required that each separate component is effective. “In the case of phages, such an approach would probably fail in many cases, because bacteria would develop resistance to some or all of the individual phages when administered individually,” they warn, explaining that combinations are necessary to have success. With safety in mind, they believe that the use of these entities as medicine for more than a century and the fact that they infect bacteria, but not human cells, implies that these treatments should be safe.
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