Science - April 22, 2012

How bacteria break down viruses

Wageningen microbiologists have figured out how bacterial defence systems destroy their enemies. They are the first to succeed in simulating this process in the laboratory.

Only DNA which is taut - like when a rubber band is twisted - is inspected by the CRISPR system.
The researchers published their findings last Thursday in the journal Molecular Cell, thereby unravelling most of the mechanisms behind the bacterial defence system. In 2008, the Laboratory of Microbiology had already discovered that a lot of bacteria have a defence system, dubbed CRISPR. This system is able to pick out invading viruses by their DNA and then destroy them. What so special about this is that the bacteria store this knowledge in their hereditary material, enabling their offspring to be protected as well. Although this defence process had already been known to a certain extent, the destruction of viruses can now be clearly explained in detail.
Demolition hammer
The protagonist and demolition hammer, so to speak, of the virus is the protein Cas3. As soon as the defence system picks out a known hostile virus, Cas3 binds itself to one of its DNA strands and cuts through it. Subsequently, demolition by the hereditary material is carried out bit by bit until the invader can no longer build any more new viruses. 'We have been doing experiments for many years, but have not succeeded until now,' says Edze Westra, a researcher at the Laboratory of Microbiology. It had seemed impossible to reproduce a stable Cas3 earlier on. The breakthrough came when the protein was fused with its natural partner. That required a bit of manoeuvering. 'But,' says Westra, 'that's how nature works sometimes, so it's pretty close to the real situation.'
Rubber band
Much has also been known about how bacteria get the enemy within range, says Westra. The main player in the CRISPR system is the protein complex Cascade, which scans DNA strands continuously to compare the code with known viral codes. However, this detection activity does not cost the bacteria any energy at all. Westra is the first who can explain why. Cascade only binds DNA that is 'taut', like when a rubber band is twisted. Cascade then uses the energy available in this taut situation to separate and read the DNA strands. There is still one big blank in the CRISPR system: no-one knows how viral DNA codes used by the bacteria in the detection can get into the bacteria genome. We would have to wait patiently for an answer to this question, says Westra, but work is underway.