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USA: Bacteriology How Viruses Disable Bacterial Immune Systems

| Editor: Alexander Stark

For the first time, researchers have solved the structure of viral anti-Crispr proteins attached to a bacterial Crispr surveillance complex, revealing precisely how viruses incapacitate the bacterial defense system.

Crispr surveillance complex is disabled by two copies of anti-Crisprprotein AcrF1 (red) and one AcrF2 (light green). These anti-Crispr's block access to the Crispr RNA (green tube) preventing the surveillance complex from scanning and targeting invading viral DNA for destruction.
Crispr surveillance complex is disabled by two copies of anti-Crisprprotein AcrF1 (red) and one AcrF2 (light green). These anti-Crispr's block access to the Crispr RNA (green tube) preventing the surveillance complex from scanning and targeting invading viral DNA for destruction.
(Source: Lander Lab)

La Jolla/USA — For many bacteria, one line of defense against viral infection is a sophisticated RNA-guided “immune system” called Crispr-Cas. At the center of this system is a surveillance complex that recognizes viral DNA and triggers its destruction. However, viruses can strike back and disable this surveillance complex using “anti-Crispr” proteins, though no one has figured out exactly how these anti-Crispr's work — until now.

The research team, co-led by biologist Gabriel C. Lander of The Scripps Research Institute (TSRI), discovered that anti-Crispr proteins work by locking down Crispr’s ability to identify and attack the viral genome. One anti-Crispr protein even “mimics” DNA to throw the Crispr-guided detection machine off its trail. “It’s amazing what these systems do to one-up each other,” said Lander. “It all comes back to this evolutionary arms race.”

The new research, co-led by Blake Wiedenheft of Montana State University, was published recently in the journal Cell. (Link to the publication)

If Crisp complexes sound familiar, that’s because they are at the forefront in a new wave of genome-editing technologies. Crisp (pronounced “crisper”) stands for “clustered regularly interspaced short palindromic repeats.” Scientists have discovered that they can take advantage of Crispr’s natural ability to degrade sections of viral RNA and use Crispr systems to remove unwanted genes from nearly any organism.

“Although Crispr-Cas9 is the ‘celebrity’ Crispr system, there are 19 different types of Crisp systems, each of which may have unique advantages for genetic engineering. They are a massive, untapped resource,” said Lander. “The more we learn about the structures of these systems, the more we can take advantage of them as genome-editing tools.”

Bacteria and Viruses Locked in an Arms Race

Using a high-resolution imaging technique called cryo-electron microscopy, the researchers discovered three important aspects of Crispr and anti-Crispr systems.

First, the researchers saw exactly how the Crispr surveillance complex analyzes a virus’s genetic material to see where it should attack. Proteins within the complex wrap around the Crispr RNA like a grasping hand, exposing specific sections of bacterial RNA. These sections of RNA scan viral DNA, looking for genetic sequences they recognize.

“This system can quickly read through massive lengths of DNA and accurately hit its target,” said Lander. If the Crispr complex identifies a viral DNA target, the surveillance machine recruits other molecules to destroy the virus’s genome.

Next, the researchers analyzed how viral anti-Crispr proteins paralyze the surveillance complex. They found that one type of anti-CRISPR protein covers up the exposed section of Crispr RNA, thereby preventing the Crispr system from scanning the viral DNA.

(ID:44610366)