Primitive bacterial parasites were first to use CRISPR to combat against one another

Humans are not the first to leverage the benefits of CRISPR. Pioneering research at the University of Copenhagen (UCPH) has redefined what CRISPR is and its applications.

Primitive bacterial parasites were first to use CRISPR to combat against one another
Rafael Pinilla-Redondo. Image Credit: University of Copenhagen.

Scientists from UCPH have found that primordial bacterial parasites use CRISPR as a weapon to fight against one another. This finding paves the way to reprogram CRISPR to combat multi-drug resistant bacteria.

In the recent past, the advent of CRISPR technologies, specifically gene-editing scissors, has proven revolutionary. Researchers have, in fact, understood ways to exploit these natural systems in the field of biotechnology and pharmaceutical industries, apart from other areas.

A new study at the University of Copenhagen demonstrates that humans were not the first to identify ways to leverage the advantages of the CRISPR technique. Evidently, it has been exploited by primordial bacterial parasites for millions of years.

The researchers investigated Type IV CRISPR-Cas—the least described and most mysterious among the six CRISPR-Cas systems that occur in nature. They revealed characteristics that vary entirely from those in other systems.

Redefining CRISPR

Until recently, CRISPR-Cas was believed to be a defense system used by bacteria to protect themselves against invading parasites such as viruses, much like our very own immune system protects us. However, it appears that CRISPR is a tool that can be used for different purposes by diverse biological entities.”

Rafael Pinilla-Redondo, PhD, Department of Biology, University of Copenhagen

Plasmids are one of these biological entities. They are small DNA molecules that usually act like parasites and, similar to viruses, need a host bacterium for survival.

Here we found evidence that certain plasmids use type IV CRISPR-Cas systems to fight other plasmids competing over the same bacterial host. This is remarkable because, in doing so, plasmids have managed to turn the system around. Instead of protecting bacteria from their parasites, CRISPR is exploited to perform another task.

Rafael Pinilla-Redondo, PhD, Department of Biology, University of Copenhagen

He added, “This is similar to how some birds compete for the best nesting site in a tree, or how hermit crabs fight for ownership of a shell.”

“A humbling realization”

The finding defies the opinion that CRISPR-Cas systems have only one function in nature, which is to behave as immune systems in bacteria.

Rafael Pinilla-Redondo said that this finding offers certain additional points of view: “We humans have only recently begun to exploit nature’s CRISPR-Cas systems, but as it turns out, we are not the first. These ‘primitive parasites’ have been using them for millions of years, long before humans. It is quite a humbling realization.”

Benefits of CRISPR

According to the researchers, these systems could be employed to fight against multi-drug resistant bacteria (MDR)—one of the greatest threats to humans. Each year, MDR bacteria cause hundreds and thousands of death.

Bacteria turn antibiotic-resistant by acquiring genes that render them resistant to treatment with antibiotics. This condition often occurs when antibiotic-resistant genes from one bacterium are transferred by plasmids to another bacterium.

As this system appears to have evolved to specifically attack plasmids, it is plausible that we could repurpose it to fight plasmids carrying antibiotic resistant genes. This could be achieved because it is possible to program CRISPR to target what one wants

Rafael Pinilla-Redondo, PhD, Department of Biology, University of Copenhagen

Source:
Journal reference:

Pinilla-Redondo, R., et al. (2020) Type IV CRISPR-Cas systems are highly diverse and involved in competition between plasmids. Nucleic Acids Research. doi.org/10.1093/nar/gkz1197.

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