Scientists are a step closer to understanding the microbial world with a new discovery they say may allow safer gene editing, and lead to more alternatives to antibiotics.
A study published in Nature, conducted by an international team of researchers and lead by Professor Peter Fineran from the University of Otago, New Zealand, and Dr Rafael Pinalla-Redondo from the University of Copenhagen, Denmark, reveals new ways viruses suppress bacteria’s defence systems.
CRISPR-Cas are immune systems that protect bacteria from bacterial viruses called bacteriophages, which inject their genetics into specific bacterium to replicate.
A bacterium’s CRISPR-Cas immunity works by taking pieces of phage DNA and adding them to the bacterium’s genome. The DNA is remembered by the bacterium so that later it can identify if that specific phage attacks again.
Co-author Dr David Mayo-Muñoz, from the Department of Microbiology and Immunology at University of Otago, explains.
“If a virus comes in, part of its DNA is added to the memory bank, and then turned from DNA to RNA in the process. Each RNA acts like a guide so the CRISPR-Cas system can correctly identify and destroy the invading phage. Each addition to the memory bank is divided by a CRISPR repeat sequence, which stacks up like bookends between each phage sequence,” says Mayo-Muñoz.
Phages have evolved in varying ways to overcome the bacterium’s CRISPR-Cas system.
“Bacteria have CRISPR-Cas so the phages have developed anti-CRISPRs, which enables them to block the immune complexes of the bacteria. What we’ve discovered is a whole new way that phages can stop CRISPR-Cas systems,” says Mayo-Muñoz.
Previous research has shown that some phages have CRISPR repeat sequences in their genomes. The new study demonstrates that phages load bacteria with these RNA repeats to stop CRISPR–Cas.
“Phages have components of bacterial CRISPR-Cas systems in their own genomes. They use these as molecular mimics for their own benefit to silence the immune system of bacteria and allow phage replication,” says Fineran, head of the Phage-host interactions (Phi) laboratory at Otago.
CRISPR-Cas systems are used as tools by scientists to precisely edit genomes.
“To harness the potential of CRISPR-Cas technologies, it is important to be able to control it, turn it on and off, and tune it, improving its accuracy and therapeutic benefit,” says Mayo-Muñoz.
“We have the possibility to design RNA anti-CRISPRs for all CRISPR-Cas systems and their specific applications.”
Scientists’ goals for CRISPR-Cas is to repair mutated genes that cause diseases, edit genes, and offer another alternative to antibiotics.
Phages can reduce antibiotic usage with their ability to kill pathogenic bacteria, but they require the right anti-CRISPR to restrict the bacteria’s CRISPR-Cas system.
“We are excited to be able to provide a whole new insight into how phages battle with their bacterial hosts. We hope that these RNA anti-CRISPRs will provide a new approach to help control CRISPR-Cas technologies,” says Professor Fineran.
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