Bacteria & Immunity: How Ancient Defenses Benefit Humans | Science

The famous phrase says, “The blow that does not kill me makes me stronger.” And if it is used metaphorically in the human world, to indicate that challenges that do not lead to death give the individual strength and fortitude, in the world of bacteria, it goes beyond the metaphorical case, to describe a realistic and practical mechanism, according to which the blows that were intended to kill them are transformed into tools that give them more strength and fortitude.

For billions of years, bacteria and viruses have been waging a constant battle. Viruses constantly attack bacteria, and bacteria develop ways to defend themselves. This long struggle produced an amazing defense mechanism within bacteria, which is a practical translation of the famous phrase.

A research team from the University of Pennsylvania discovered this mechanism, which was previously neglected, within some strains of E. coli bacteria, and found that understanding it may help humans in several areas, most notably the development of new ways to fight bacteria, especially with their increasing resistance to antibiotics.

What is this mechanism?

The story of this defense mechanism begins with bacteria being exposed to continuous attacks from viruses known as “phages.” Some of these phages follow a different plan. They do not destroy the cell immediately, but rather live inside it quietly, waiting for the appropriate conditions to attack.

But in some cases, these viruses completely lose the ability to attack and turn into what scientists call “stealth phages,” which are viral remains that do not die or function, but remain.

What is new that scientists discovered in the study published in the journal “Nuclear Acids Research” is that over time, bacterial generations inherited this silent virus within their genes, without it causing any harm.

The bacteria did not leave this viral legacy useless, but rather developed a smart mechanism that exploits these remains to its advantage. When it is exposed to a new attack from another virus, it activates parts of the old viral DNA, producing defensive proteins that prevent the attacking virus from attaching to the cell or penetrating it.

How does the defense mechanism work?

In their study, the researchers describe this mechanism, which begins to be activated when a new virus approaches and attempts to land on the surface of the bacteria to begin the attack.

At the first attempt to touch, an alarm signal sounds inside the cell, as an enzyme specialized in recombination, “BenQ,” enters the scene, which is like an emergency genetic engineer intervening to the rescue, as it begins carrying out a precise movement inside the DNA of the bacteria called “genetic inversion,” that is, inverting a small part of the genetic code, specifically the part that contains traces of the old virus.

With this movement, a genetic page that was dormant is opened, and the bacteria activate new instructions that were not previously read, and the result is the manufacture of hybrid proteins, which are a mixture of bacterial genes and the remains of old viral genes.

These hybrid proteins head to the cell surface and reshape the bacterial receptors, which are the points on which the attacking virus depends for attachment and injection. Suddenly the new virus finds itself facing an unknown surface that it cannot recognize, and thus the viruses that tried to land find no door or window, and thus the defense has succeeded before the attack begins.

Practical experiment on E. coli bacteria

The researchers tested this mechanism by increasing the production of hybrid proteins in E. coli bacteria, then exposing them to viruses and leaving them overnight. After that, they measured the turbidity of the solution. The higher the turbidity, the less the presence of viruses. They also conducted computer modeling to simulate the adhesion of viruses to bacteria, and confirmed the validity of their results through experiments.

Professor Thomas Wood, Professor of Chemical Engineering at the University of Pennsylvania, and the lead researcher of the study, says – in a statement published on the university’s website – that when we increase the production of the defense protein, we succeed in preventing the virus from attaching to the bacteria at first, “but after 8 experimental cycles, the virus succeeds in developing new landing proteins that enable it to bypass the defense.”

Wood emphasized that these results improve understanding of the natural defense mechanisms of bacteria, which can be used with beneficial bacteria that are used in industries such as cheese and yogurt, and also combat pathogenic species that are resistant to antibiotics. He added that the team will continue to study 8 other “hidden phages” to find out their potential role in defense.