Researchers at Rockefeller University have found that Staphylococcus aureus bacteria are able to resist viruses. The results are published in the journal Molecular Cell.
The bacterium’s strategy is quite interesting: once a staphylococcus sees a virus, it can use a variety of immune strategies to cut its genome with molecular cutters like CRISPR-Cas.
However, new research shows that bacteria’s defense strategies work in tandem. The scientists found that there is a surprising level of cooperation between the CRISPR-Cas system and another important bacterial defense strategy known as restriction enzymes.
Both types of bacterial protection have been studied for a long time. In the 1970s, scientists used restriction enzymes to develop a new tool called recombinant DNA that made it possible to clone and study individual genes. And 10 years ago, technology based on CRISPR-Cas revolutionized bioscience by providing scientists with the means to edit genomes in living cells and organisms.
Only now, however, scientists have discovered that the bacteria’s virus-killing strategies work better together than they do individually. When staphylococci are protected only by restriction enzymes, their protection is short-lived because some viruses will eventually start to protect their DNA – and after a while, as their study shows, the bacteria growing in the dishes will begin to decrease. If the bacterium has access to both systems, it quickly recovers.
The results of the study show that restriction enzymes serve two functions: they act as the first line of defense and prepare the material needed by CRISPR-Cas to accurately target the virus. Restriction enzymes are able to cleave short DNA sequences, so the bacterium uses them as soon as the virus enters the bacterial cell. CRISPR-Cas, a more sophisticated system, will come later. The segments, previously truncated by restriction enzymes, help the CRISPR-Cas engine generate the molecular landmark needed to find viruses and stop infection.
“This mechanism is reminiscent of our own multi-pronged immune response,” Marraffini says. “This includes a temporary first line of defense before activating a second, more robust adaptive response.”
“It’s a bit like getting vaccinated,” says Marraffini. “The restriction enzyme cuts small pieces of the virus, which CRISPR will then use to create an adaptive response.”
The findings may not only help to understand how staphylococcus protects itself from viruses. This gives scientists a chance to better prepare to defend themselves against staph itself, a species known for its ability to become resistant to antibiotics.
Last year, Marraffini’s team discovered that the bacterium uses its CRISPR-Cas system not only to defend itself against viruses, but also to develop multidrug resistance. A better understanding of the system may one day allow scientists to manipulate it with drugs to fight staph infections that defy any other treatment.