Bacteria use CRISPR / Cas system to evade host immune system

Bacteria use CRISPR / Cas system to evade host immune system

Clustered regularly interspaced short palindromic repeat sequences (CRISPR) is a genetic system used by bacteria to fight viruses. In a new study, a study from Emory University in the United States The staff found that CRISPR was involved in assisting some bacteria to evade the mammalian immune system.

Bacteria use CRISPR for self-protection. Its function was originally discovered by dairy industry researchers trying to prevent bacteriophages (viruses infected with bacteria) from destroying the bacterial culture used to make cheese and yogurt. The bacteria will come from small bacteriophages The fragments of DNA are integrated into their own CRISPR region, and the information obtained by ingesting the phage's DNA prevents the invasion of these viruses.

Now, in this new study, the researchers confirmed that the new killer Francisella novicida (F. novicida), who is closely related to a bacterium that causes rabbit fever and another bacterium that causes meningitis, needs Part of the CRISPR system to maintain infectivity. F. novicida, a bacterium that grows in mammalian cells, uses a part of the CRISPR system to shut down a bacterial gene so that their hosts evade detection and destruction triggered by this gene.

Prior to this, scientists have discovered that the loss-of-function CRISPR system produces a weakened bacterial strain, which makes it easier for the immune system to recognize it. This discovery may accelerate vaccine development. But this new study also suggests that In biology, defensive tools can be used to evade.

The author of the paper, Dr. David Weiss, an assistant professor of medicine at Emory University School of Medicine, said, "The CRISPR system is a bacterial defense system, but we found that bacteria can actively use it to evade recognition by the host's immune system, resulting in disease."

When working as a postdoctoral fellow with Denise Monack, a professor at Stanford University, Weiss first isolated the F. novicida strain with a flawed CRISPR system. F. novicida infects rodents, and only in rare cases infects humans. It It is a model for studying the more dangerous Francisella tularensis (F. tularensis), in which F. tularensiss is a potential biological weapon. Prior to this, Weiss has been searching in F. novicida to cause live Genes that play an important role in the disease of animals.

Weiss said, "Gene mutations play a stronger role in bacteria. Wild-type F. novicida strain can kill mice, but its mutant strain will be cleared after a few days in mice. But why do these bacteria need Can resistance to foreign DNA cause illness in mice? That makes no sense. "

In the current study, the researchers found that when F. novicida infects mammalian cells, they need a gene in the CRISPR system to turn off the production of a lipoprotein (a part of the bacterial cell membrane). This lipoprotein can activate Mammalian immune cells. Therefore, in order to continue to survive and not be detected by the immune system, they have to prevent the production of fat white.

We carefully analyzed which part of the CRISPR system is necessary to turn off this lipoprotein. This CRISPR system is composed of several protein-coding genes, and also integrates a small piece of DNA from the phage as a repeat sequence into this kind of In bacterial DNA, the RNA-directed enzyme Cas9 produced by this repetitive sequence cuts the phage DNA into fragments.

For example, some streptococci and Listeria have similar CRISPR systems, but scientists have not yet discovered that this system has any potential role in the process of these bacteria causing human illness. Weiss and Sampson plan to further study how Cas9 It works to shut down how the lipoprotein gene of F. novicida and Cas9 are activated.