Scientists at the University of Otago in New Zealand say they have discovered how viruses that specifically kill bacteria can outwit bacteria by hiding from their defenses. These findings are important for the development of new antimicrobials based on viruses and provide a significant advance in biological knowledge, according to the researchers.
Lead researcher Peter Fineran, PhD, professor, explained that the rise in multi-drug resistant bacteria is leading to the development of alternative therapeutics, including viruses (bacteriophages) that specifically kill bacteria. However, bacteria can become resistant to phages.
Phages are the most abundant biological entities on the planet and are important for global ecosystems, but they can also be used to kill bacterial pathogens, continued Fineran. To defend themselves from the phage invasion, bacteria have developed CRISPR-Cas defense systems, but the phages have come up with ways to avoid these bacterial defenses.
In the study, (“A jumbo phage that forms a nucleus-like structure evades CRISPR–Cas DNA targeting but is vulnerable to type III RNA-based immunity”) published in Nature Microbiology, the University of Otago team discovered a widespread method used by phages to hide from bacterial defenses. They discovered a “jumbo” phage which, as the name suggests, is very big, with hundreds of genes. This phage is not recognized by CRISPR-Cas defenses that would normally cut up the genetic DNA instructions to make many new phages.
“CRISPR–Cas systems provide bacteria with adaptive immunity against bacteriophages. However, DNA modification, the production of anti-CRISPR proteins, and potentially other strategies enable phages to evade CRISPR–Cas. Here, we discovered a Serratia jumbo phage that evades type I CRISPR–Cas systems, but is sensitive to type III immunity. Jumbo phage infection resulted in a nucleus-like structure enclosed by a proteinaceous phage shell—a phenomenon only reported recently for distantly related Pseudomonas phages. All three native CRISPR–Cas complexes in Serratia—type I-E, I-F, and III-A—were spatially excluded from the phage nucleus and phage DNA was not targeted,” the investigators wrote.
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Thanks to Heinz V. Hoenen. Follow him on twitter: @HeinzVHoenen