Weizmann Institute of Science scientists have discovered a bacterial immune system that "neuters" the tails of viruses. The new system is based on a protein previously discovered by Nobel laureates Avraham Hershko and Aharon Chachanover
Viruses that attack bacteria - phages - have a head and a tail. While the head contains the genetic material of the virus, the tail is used to identify a potential host, i.e. a bacterial cell, and inject it with the genetic material. After the injection, the phage takes over the mechanisms of the host bacterium and causes it to produce new copies of the phage, which eventually explode the cell, and go out to infect other bacteria in the colony. In a new study Published today in the scientific journal Nature Weizmann Institute of Science scientists reveal a bacterial immune system that disrupts the phage's plot by attaching a small protein molecule to the end of its tail. The components of the new system are structurally similar to a human defense mechanism, and may explain its evolutionary origin.
Since the discovery of the first defense mechanisms of bacteria against phages in the 60s until recently, only a small number of bacterial immune systems that harm viruses were known - the most famous of which is CRISPR-Cas9, whose discovery revolutionized the field of genetic editing. However, in recent years there has been a wave of new discoveries in the field, in which more than 150 new bacterial vaccine systems with diverse mechanisms of action have been revealed. A significant part of the systems were revealed by a method developed in the laboratory of Prof. Rotem whistles in the department of molecular genetics at the institute, and works according to a simple principle - genes related to immune defense mechanisms in bacteria tend to cluster together in the bacterial genome in areas called "defense islands". The researchers scan genes whose function is unknown and are located near known defense islands, thus revealing new immune systems. "We recognize in the bacterial immune systems familiar components from immune mechanisms that have been well studied in humans," describes Prof. Sorek. "The knowledge we have gained shows that the evolutionary origin of a large part of our innate immune system is bacteria."
Ubiquitin on the shoulders of giants
In the 70s, a cellular control system was discovered for the first time that can change the structure and function of proteins as well as their lifespan, all through the attachment of a small protein called ubiquitin to the target protein. Since the discovery, which earned Professors Aharon Chachanover, Avraham Hershko and Irwin Rose the 2004 Nobel Prize, many ubiquitin-like systems have been discovered, in which enzymes attach small proteins of various types to target proteins and thereby change their fate. One of the mysterious proteins in the human immune system is a ubiquitin-like protein called ISG15. This protein has a role in protecting against various viruses such as influenza and HIV, but it is not entirely clear how it performs its task.
""The knowledge we have gained shows that the evolutionary origin of a large part of our innate immune system is bacteria"
In the search for new bacterial immune systems in Prof. Sorek's laboratory, an immune system coded in the genome of many bacterial strains was discovered, containing a ubiquitin-like protein similar in structure to ISG15. As part of the new research, which was led by Dr. Jens Hor, the scientists discovered that unlike other bacterial immune systems, the system that was discovered does not prevent the viruses from taking over the cell and producing new copies of themselves, but somehow knows how to stop their spread to other cells in the colony.
In order to understand how the replicated viruses lost their infectivity and how the discovered immune system contributed to this, Prof. Sorek's research group teamed up with Dr. Sharon Wolf, head of the electron microscope unit in the chemical research infrastructure department at the institute. The researchers marked the ubiquitin-like protein on which the system is based with gold particles that are clearly visible through a microscope, and were amazed when they looked at the scans of the replicated phages: the protein in question was located at the end of the viral tail and thus prevented the phages from using their tails to locate bacterial cells and infect them. The scientists estimate that the new defense system they discovered knows how to recognize the three-dimensional structure of the virus tail, and is therefore able to act effectively against very different phages with one central common denominator: a similar tail structure.
"Our work in bacteria can inspire human immune system researchers to test whether a similar principle applies to the human immune protein ISG15. Viruses that attack humans do not have a tail, but it is possible that the system disrupts a central structural protein of the virus there as well," says Prof. Sorek. "The immune system we studied is just one of a series of systems we have identified in the genome of bacteria that include ubiquitin-like proteins. Now it remains to be discovered how the rest of the bacterial systems fight their old enemies: the viruses."
More of the topic in Hayadan:
