Altruistic Viruses? Phages Fight Back Against CRISPR Defenses In Bacteria

By Vicky Stein

Black and white science image of phages
The phages in this electron micrograph are viruses that target bacteria. They can create anti-CRISPR proteins to fight bacterial immune systems. Credit: Joseph Bondy-Denomy

Although CRISPR has made headlines as a powerful system for editing genes, it actually evolved as way for bacteria to defend themselves against infection by viruses. While viruses inject their genetic material into a bacterium, CRISPR lurks inside, ready to recognize and destroy the invading viral genes before they do any damage. Viruses, the other half of this evolutionary war, have evolved their own counterattacks. Their weapons are known as anti-CRISPRs. Now, scientists think they are beginning to understand how these tiny battles play out. 

Joseph Bondy-Denomy, PhD, discovered anti-CRISPRs as a graduate student, and is now an assistant professor in the Department of Microbiology and Immunology at UCSF. Adair Borges, a graduate student working in his lab, recently discovered what the two researchers are calling a form of “viral altruism,” as described in a new paper in Cell.

Phages, viruses that attack bacteria, face a difficult task in breaking through the CRISPR defenses inside of a bacterial cell. One phage isn’t going to get the job done – but many phages might, Borges and Bondy-Denomy found. Each marauding virus can force the cell’s internal machinery to produce a small amount of the anti-CRISPR protein encoded in the viral genetic material before the CRISPR system slices it apart. If enough viruses attack, they can overwhelm a cell’s CRISPR defenses before the cell can replenish them; many viruses must perish before one lucky phage eventually breaks through and takes over the cell. 

This kind of self-sacrificing behavior has long been a subject of study in the animal kingdom: For example, most female ants in a hive raise and care for their sisters, helping their mother – the queen – reproduce. As a whole, the hive is more likely to survive and grow, but almost every female ant dies without offspring.

“But this is, to our knowledge, the first example of viral altruism: in order for one virus to live, its clones have to die,” said Borges. “When the phages have the odds stacked against them, they don’t deploy a clever mechanism. They just fail enough for one of them to survive.”

Gene Editing and CRISPR

Gene editing is already providing new therapies for rare diseases that just a generation ago were untreatable. New techniques with CRISPR hold promise for greatly improving both quality and length of life for those suffering from genetic conditions.

Illustration of people constructing a strand of DNA