Phages fight back: how anti-CRISPRs interfere with the bacterial immune system

A transmission electron micrograph of phage JBD93, which contains an anti-CRISPR gene. (Credit: Joe Bondy-Denomy)
A transmission electron micrograph of phage JBD93, which contains an anti-CRISPR gene. (Credit: Joe Bondy-Denomy)

So nat’ralists observe, a flea
Hath smaller fleas that on him prey;
And these have smaller fleas to bite ‘em.
And so proceeds Ad infinitum.

Jonathan Swift, 1733

When the Anglo-Irish satirist wrote these words nearly two centuries ago, he could not have known just how far down the tree of life his observations would hold true. These predator-prey relationships exist beyond the plains of Africa or the jungles of Borneo. They extend to the realm of microscopic organisms and to the world of bacteria and the teeny tiny, itsy bitsy viruses that prey on them. These viruses are called bacteriophages, or phages for short.

Like human and other animal viruses, phages rely completely on their host for reproduction. They enter a bacterial cell and hijack the cellular machinery to make new phages until the cell is literally bursting with viral cargo. A torrent of phages is unleashed that go on to infect more bacteria and continue the cycle.

But bacteria are not helpless victims in this story. They have a large arsenal of anti-phage weapons to keep phages out and prevent them from taking over. Perhaps the coolest of these weapons is the CRISPR-Cas system. First discovered in 2007, the CRISPR-Cas system functions as the bacteria’s immune system. It is both a memory keeper and a hitman. Every time a bacteria survives a phage infection (which doesn’t happen often), the CRISPR-Cas complex takes a small piece of phage DNA and adds it to the bacteria’s own DNA, gradually building a database of unique DNA fingerprints from every phage that has ever tried to kill it. In other words, bacteria with CRISPR-Cas systems are able to “learn” from their previous phage encounters and acquire immunological memory based on those experiences—a trait that was previously thought to be unique to animals.

“It’s the first example of a single cell, simple [bacteria] having an adaptive immune system,” says Dr. Joseph Bondy-Denomy, a faculty fellow at the University of California, San Francisco. “The adaptability of CRISPR is very, very rapid. I think that’s why it’s so exciting.” Continue reading