Bacterial Retrons Found to Serve as Anti-Phage Defense

In a study published today in Cell, scientists report that retrons are immune system guards that ensure the survival of the bacterial colony when it is infected by viruses. In addition to uncovering a new strategy used by bacteria to protect themselves against viral infection, the research revealed many new retrons that may, in the future, add to the genome-editing toolkit.

The team at the Weizmann Institute of Science didn’t originally set out to solve the retron mystery; they were seeking new elements of the bacterial immune system, specifically elements that help bacteria to fend off viral infection. Their search was made easier by their recent finding that bacteria's immune system genes tend to cluster together in the genome within so-called defense islands. When they uncovered the unique signature of retron within a bacterial defense island, the team decided to investigate further.

Their initial research showed that this retron was definitely involved in protecting bacteria against the viruses known as phages that specialize in infecting bacteria. As the researchers looked more closely at additional retrons located near known defense genes, they found that the retrons were always connected to one other gene. When either the accompanying gene or the retron was mutated, the bacteria were less successful in fighting off phage infection. The researchers then set out to look for more such complexes in defense islands. Eventually, they identified some 5,000 retrons, many of them new, in different defense islands of numerous bacterial species.

To check if these retrons function, generally, as immune mechanisms, the researchers transplanted many retrons, one by one, into laboratory bacterial cells that were lacking retrons. As they suspected, in a great number of these cells they found retrons protecting the bacteria from phage infection. Further investigation showed that retrons do not sense the phage invasion itself, but rather keep watch on another part of the immune system known as RecBCD, which is one of the bacterium's first lines of defense. If it realizes that the phage has tampered with the cell's RecBCD, the retron activates its program through the second, linked genes to kill the infected cell and protect the rest of the colony.