A groundbreaking study reveals a new regulatory mechanism in phage proteins, opening new avenues for understanding bacterial defense mechanisms and developing phage-based therapies.
A surprising discovery has facilitated significant advancements in combating dangerous bacteria. An international group of scientists, led by Professor Peter Fineran from the University of Otago, studied a specific protein employed by phages, which are viruses that infect bacteria.
Research into this microscopic arms race between bacteria and phages is important as it can lead to alternatives to antibiotics. Published in the prestigious international journal Nature, the study analyzed a protein phages use when deploying anti-CRISPR, their method of blocking the CRISPR–Cas immune system of bacteria.
Lead author Dr Nils Birkholz, of Otago’s Department of Microbiology and Immunology, says understanding how phages interact with bacteria is an important step on the path to using phages against bacterial pathogens in human health or agriculture.
“Specifically, we need to know about the defense mechanisms, such as CRISPR, that bacteria use to protect themselves against phage infection, not unlike how we use our body’s immune system against viruses, and how phages can counteract these defenses. For example, if we know how phages kill a specific bacterium, this helps identify appropriate phages to use as antimicrobials. More specifically, it is important to understand how phages control their counter-defense arsenal, including anti-CRISPR, upon infection – we must understand how phages regulate the expression of genes that are useful in their battle against bacteria,” he says.
Discovery of a Versatile Protein Domain
The research revealed just how carefully phages need to deploy their anti-CRISPRs.
“We already knew that a particular phage protein has a part, or domain, that is very common in many proteins involved in gene regulation; this helix–turn–helix (HTH) domain is known to be able to bind DOI: 10.1038/s41586-024-07644-1