The new system was discovered in bacteria - but is also used in corals, bees and others
Every time we call, send a WhatsApp or watch a video, some of the energy stored in our mobile phone battery is dissipated. Living cells also store energy in coins that they can redeem when needed to implement life processes. The central energy currency of all life forms on earth - that is, the "lithium battery" of the animal world - is the famous ATP molecules. Now it turns out that not only loading the cell with ATP molecules is essential, also getting rid of them may be life saving. In a new study published today in the scientific journal Cell, Weizmann Institute of Science scientists revealed a new family of proteins that drains bacteria of energy and thus protects them from invaders. The researchers showed that this unknown immune mechanism is found not only in single-celled organisms, but it has been preserved throughout more than a billion years of evolution and is used by many animals - from bees to corals.
This new mechanism is the latest chapter in a series of more than 100 sophisticated immune systems that have been discovered in recent years and are used by bacteria in their billions of years of heroic struggle against phages - viruses that attack bacteria. Many of these systems were discovered and deciphered in the laboratory of Prof. Rotem whistles in the Department of Molecular Genetics at the Weizmann Institute of Science. Similar to the viruses that infect us, phages also consist of a few proteins and a lot of genetic material - DNA or RNA - which they insert into bacteria in order to take control of them. After taking over, the viruses take advantage of the bacteria's cellular production mechanisms to replicate themselves again and again. When they consume the resources of the individual bacterium, they tear the cell envelope, break out and spread in the bacterial colony.
In their new study, the researchers focused on a gene that caught their attention, as its activation mysteriously prevented the ability of phages to replicate and spread in the bacterial colony. They revealed that the mysterious gene codes for a protein that cuts and permanently destroys ATP molecules, thus depriving the invading phage of the energy needed for its replication - an immune mechanism previously unknown in nature. The scientists concluded that the gene played a crucial role in the bacterial immune system, as in its absence, phages that infected bacteria replicated at a rate 100 times faster.
"Lowering the ATP levels in the cell is an ingenious mechanism in its simplicity," explains Dr. Francois Rousse, who led the research team in Prof. Sorek's laboratory. "The phage cannot reproduce without energy, and for the bacteria, which is infected and about to die anyway, it is better to drain the battery and not allow the phage to reproduce and spread to the rest of the colony." The researchers also discovered that in some cases the breakdown of ATP affects the control mechanisms of the phage and causes them to tear the bacterial cell envelope too early, before the phage had time to replicate, thus preventing extensive damage to the colony.
""This is a genius mechanism in its simplicity. The phage cannot reproduce without energy, and for the bacterium, which is going to die anyway, it is better to drain the battery and not allow the phage to reproduce and spread to the rest of the colony."
Surprisingly, this unknown mechanism is more common than one might imagine: the researchers scanned a genomic database of tens of thousands of bacteria and found more than a thousand immune genes that work in a similar mechanism. Moreover, the scientists were surprised to find the unique ability to break down ATP also in a family of proteins that were not known to belong to the cell's immune system. This is how the researchers discovered a new immune system that is found in hundreds of different bacteria, and provides effective immune protection against viruses.
But the research did not stop only at bacteria: from a comprehensive test carried out by the researchers it emerged that immune proteins that cut ATP are also produced in much more developed organisms - fungi, various insects, including bees, corals, sponges and many other organisms. These types of immune proteins do not exist in human cells, but the researchers believe that they are probably the ancestors of proteins that make up our innate immune system.
"Many studies in recent years have used knowledge about immune systems in evolved organisms in order to discover new immune mechanisms in bacteria," says Prof. Sorek. "Our research, alongside the vast body of knowledge that has accumulated on immune systems in bacteria, allows us today to start operating from the opposite logic - to learn from bacteria about the innate immune systems of complex animals. ATP molecules are among the most common in nature, and therefore understanding their immune function is of great value in deciphering the defense strategies of countless living creatures against viruses that attack them."
Erez Yermia, Shahar Nesher, Dr. Adi Milman and Sara Melamed from the department of molecular genetics at the institute also participated in the study; Dr. Alexander Brandis, Tebi Melman, Dr. Sergey Malitsky and Dr. Maxim Itkin from the Department of Life Science Research Infrastructures at the institute.
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