Today we will talk about another type of virus, viruses that do not infect people, but other microorganisms: bacteria. What are we talking about? KEEP READING!

What is a bacteriophage? A bacteriophage, also known as phage, is a virus that instead of infecting humans, animals, or plants, specifically infects bacteria. Yes, we are not the only ones, bacteria also fear viruses.

This type of virus does not differ much from humans, in fact, the structure is practically the same: a little genomic material (some only have 3 genes) and an envelope that protects it. In some cases, the continent may be more extravagant, but the content remains the same.

And watch out, because although bacteriophages seem like a novel discovery, they have been known since 1896, although they were not named as such, by d’Herelle, until 1917.

How do these bacteriophages work? They are obligate parasites (like the rest of viruses, come on). This term comes to mean that they have to infect other organisms in order to spread, in this case, bacteria. And to understand how they infect a bacterium, we have to imagine the mechanism of action of a syringe. These bacteriophages bend their “paws”, bend down and act like a syringe: they inject their genetic material into the bacteria.

And from here, everything is very similar to what happens with human viruses. That genetic material, be it DNA or RNA, will use the mechanisms that copy the bacterium’s genome to generate copies of itself. The more copies you make, the more new viruses can be generated (in the end only one copy is needed per “child” virus).

And as with our viruses, bacteriophages can perform lytic, lysogenic, or a combination of both.

The result for the bacterium of a lytic phage? Lysis. The bacterium literally ends up exploiting and releasing all these new bacteriophages that have been created inside it. Incredible true?

And in the case of a lysogenic cycle? The genetic material of the virus is introduced into the genome and there it goes unnoticed, being copied and transmitted to the new bacteria, as if they were their own genes. Thus, it expands, but in a camouflaged way. The result? All bacteria from the initial infected bacteria will have a copy of the phage material. These genes can be translated into proteins and generate new viruses that end up lysing all those bacteria, at any time.

But they weren’t going to be a problem for bacteria. And why am I saying this? Because bacteria can unintentionally and indirectly use these bacteriophages to transfer genes horizontally.

  • The gene transfer in bacteria can be vertical (from parent to offspring) or horizontal (between organisms of the same generation and even of a different species).

This process is called gene transduction and is only possible when the phage performs the lysogenic cycle. When the virus has a copy of its DNA or RNA inserted into the bacterium’s genome, the first thing to do is make copies. Then, each copy must produce the proteins that those genes encode, and then encapsulate the genetic material copied from the original and that each new virus must possess. Well, during this copying and encapsulation process, in addition to its own genome, the phage can pick up fragments of the bacterium’s own genetic material.

If that bacteriophage infects another bacterium and reintroduces its genes into the new host, in addition to its own, it will be introducing those that it “started” from the last bacterium it infected. Thus, this new bacterium may be receiving genes that it did not previously possess and that may be useful to it.

We already know a little more about these “bugs”. But why can bacteriophages be useful to us? To deal with so-called resistant bacteria.

As we already explained in its day, the massive and indiscriminate use of antibiotics has facilitated the selection of resistant bacteria, of superbugs. In other words, those that carry mechanisms that make them immortal to the weapon we have to end them: antibiotics. What is the problem? That the number of panresistant bacteria (insensitive to all the antibiotics that we have) increases dangerously. And if this is not beginning to be solved, it is estimated that in 2050 these superbugs will cause more deaths than the cancer itself.

For this reason, using the natural killers of bacteria for our own benefit doesn’t sound so crazy anymore, does it? In fact, if we look back, before the discovery of penicillin, phage therapy (the use of bacteriophages as treatment) was already beginning to develop. Recall that phages have been known since the late 19th century, and penicillin was discovered in 1940.

Any studies done back then? Phages against Sighella in cases of Dysentery, against Staphylococcus sp. or against Pseudomonas aeruginosa causing chronic otitis.

However, the development of these therapies as a throwing weapon against bacteria was halted with the discovery of penicillin and all the antibiotics that subsequently arrived. In fact, as of today, there are no preparations of these bacteriophages to be used as treatment in humans.

Despite this, its use has been promoted in other sectors. The use of phages to eliminate enteropathogenic bacteria (those that cause intestinal problems) in food is approved by the FDA (Food and Drugs Administration). Or even in veterinary medicine. Phage-based products are now being marketed to more safely treat bacterial infections that attack livestock. An example? Intralytix.

However, the increase in these resistant bacteria and the ineffectiveness that antibiotics are beginning to show, due to this, put bacteriophages back into the spotlight as antibacterial therapy in humans.

Bacteriophages are very specific beings that would only attack bacteria that are capable of infecting. This does not happen with antibiotics, and more so with broad-spectrum antibiotics, which are usually prescribed by your doctor or dentist to prevent, or simply, “in case what you have is caused by bacteria.” This type of antibiotics devastate where they pass, taking ahead both the pathogenic bacteria and the “good” bacteria, those that peacefully inhabit your intestine and help you, even, to manufacture nutrients, which by yourself you would not be half capable .

For this reason, despite the fact that their use in humans is not yet approved, the laboratories do not stop investigating these tiny beings, which may be useful to us, sooner rather than later, to destroy resistant bacteria.

Some examples?

Its efficacy has been proven to kill biofilms caused by Clostridium difiicile and Proteus mirabilis. The latter bacteria are involved in infections caused precisely by the formation of these biofilms in urinary catheters.

  • Biofilms are organized groups of bacteria that are arranged in the form of a cover on an object or surface of the body. These biofilms make it difficult for antibiotics to be useful, since bacteria protect each other, and it is very difficult for the drug to reach individuals in the lower layers. Bacteriphages, on the other hand, have been shown to be helpful in their destruction.

On the other hand, researchers from IDIVAL and the University of Ghent (Belgium) have studied the use of genetically altered phages against Acinetobacter baumani.

  • With this, many possibilities are opened for mutating phages for our benefit: expanding the types of bacteria that the same phage can infect, enhancing the destructive effect of phages, increasing the life time in the circulatory system … Even, it is not ruled out either , its combination with antibiotics.

Plus? The encapsulation in lipid nanoparticles of bacteriophages is being studied at the UAB and ICN2, so that they better resist stomach acidity and may increase their shelf life in the gastrointestinal tract. This strategy has been tested against Salmonella in broilers.
On the other hand, the Massachusetts Institute of Technology is studying the use of phage scaffolding. That is, bacteriophages to which viral proteins can be added that recognize some bacteria or others depending on the need. This strategy is currently being tested with phage targeting E. coli.
Surprising truth? And this is only a small vision of what must be happening in the laboratories of the world. Another important contribution? The discovery of the so-called superpropagating bacteriophages.

Researchers from the University of Miami, Florida, United States and the National Cancer Institute at Behesda, have found that certain phages have a facility to spread antibiotic resistance genes in bacteria. As mentioned earlier, bacteriophages can pluck genes from the bacterium’s genome and transport them to other bacteria. This also applies to antibiotic resistance genes, which would be counterproductive and contrary to the purpose of these phages.

In addition to this limitation, the use of phages can cause other problems

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