Researchers from the Netherlands and New Zealand's University of Otago report the discovery of a mechanism by which bacteria use the CRISPR-Cas adaptive immunity system to combat viruses and other foreign DNA invaders. They say the system steals samples of the invader's genetic material and stores them in a memory bank so it can immediately recognize future exposures and neutralize the attack. The CRISPR-Cas system can store up to 600 samples and can also pass on these memories to subsequent generations of bacteria, note the scientists.
CRISPR-Cas' role in providing immunity was only discovered in the past decade. The system creates a genetic memory of specific past infections by viruses and plasmids. It had been thought that the system had an Achilles heel because invaders that had acquired too many mutations could no longer be recognized as they did not match the stored sample closely enough.
“What we have now discovered is that while the viruses and plasmids can evade direct recognition by acquiring multiple mutations, the system is primed to quickly generate a new immunity by grabbing a new sample of the mutated genetic material,” explains Peter Fineran, Ph.D., of the department of microbiology and immunology at the University of Otago.
He adds that the system reflected the ancient and continuing co-evolutionary arms race between bacteria on one side, and viruses and plasmids on the other.
The team’s study (“Degenerate target sites mediate rapid primed CRISPR adaptation”), which appears in PNAS, has implications for improving our understanding of bacterial evolution, including the spread of antibiotic resistance genes.
“Host immunity is based on incorporation of invader DNA sequences in a memory locus (CRISPR), the formation of guide RNAs from this locus, and the degradation of cognate invader DNA (protospacer). Invaders can escape type I-E CRISPR-Cas immunity in Escherichia coli K12 by making point mutations in the seed region of the protospacer or its adjacent motif (PAM), but hosts quickly restore immunity by integrating new spacers in a positive-feedback process termed ‘priming,’” write the investigators.
“Priming is influenced by the number of mismatches, their position, and is nucleotide dependent. Our findings imply that even outdated spacers containing many mismatches can induce a rapid primed CRISPR response against diversified or related invaders, giving microbes an advantage in the coevolutionary arms race with their invaders.”
“Discovering more about exactly how bacterial immune systems combat plasmid transfer and acquisition is of considerable interest,” points out Dr. Fineran.