Scientsits have known for 35 years what certain types of bacteria are made from, yet until the Institute's discovery scientists didn't fully understand how they worked.Certain specific types of bacteria contain something called retrons which are half RNA, half single-strand DNA. In the new discovery, these retrons were found to be an important factor in the defense system of the bacteria against viral infections. After the discovery, scientists proved the use of retrons in the bacteria's ability to fend off a specific kind of viral infection. Researchers found the answer to the long-standing mystery unintentionally – and it could have major implications, as scientists now better understand a key factor in the prevention of viral infections in bacteria.These include implications within the field of biotechnology, as retrons begin with a piece of RNA which is a template for the synthesis of the DNA strand. In the retron sequence, this template can be swapped out for any desired DNA sequence and used – sometimes in conjunction with CRISPR, another tool borrowed from the bacterial immune toolkit – to manipulate genes in various ways.
The research team's initial goal was to seek new elements that help bacteria fight off viral infection.
Their research was aided by the team's own recent findings which showed that genes in bacterial immune systems tend to cluster together in the genome within something called “defense islands.” While delving into this process they uncovered the unique signature of a retron within a bacterial defense island.
Further research proved that the retron was involved in protecting bacteria against viruses that specialize in infecting bacteria, knowns as phages. According to their research, retrons fight off phages by being continuously connected – physically and functionally – to a specific other gene.
Bacteria became less successful in fighting off phage infection when either the gene or the retron were mutated.
The research team set off in search of more retron-gene complexes in the defense islands, eventually finding some 5,000 retrons - many of which were new - in the defense islands of numerous bacterial species. Prof. Sorek's team believe that these retrons could be able to provide better templates for specific gene-editing needs.
To prove the theory that retrons function as immune mechanisms, researchers transplanted retrons into bacterial cells that previously didn't contain them. Results showed that in many of the cells, retrons protected the bacteria from phage infection.
According to their research, retrons do this by causing the infected cells to commit suicide. The strategy only works however if the suicide mechanism works faster than the virus makes copies of itself and spreads to other cells.
“It’s a clever strategy, and we found it works in a similar way to a guard mechanism employed in plant cells,” said Prof. Sorek.
“Just like viruses that infect plants, phages come equipped with a variety of inhibitors to block assorted parts of the cell immune response. The retron, like a guard mechanism known to exist in plants, does not need to be able to identify all possible inhibitors, just to have a handle on the functioning of one particular immune complex."Infected plant cells apply this ‘local suicide’ method, killing off a small region of a leaf or root, in an effort to save the plant itself. Since most bacteria live in colonies, this same strategy can promote the survival of the group, even at the expense of individual members," Prof. Sorek said.The study was conducted in the lab of Prof. Rotem Sorek of the Institute’s Department of Molecular Genetics, and was led by lab members Adi Millman as part of the Ariane de Rothschild Women Doctoral Program, Dr. Aude Bernheim, and Avigail Stokar-Avihail.