This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: As antimicrobial resistance grows around the world, novel therapies to counter it become increasingly important. Phages—viruses that infect bacteria—are an exciting avenue of research in this regard, providing a means to selectively kill pathogenic bacteria, even those resistant to traditional antibiotics.
However, to utilize phages effectively, it is important to understand how they interact with their host bacteria. EMBL scientists and collaborators have discovered a new paradigm by which phages can shut down bacterial defense systems. They found that certain phages can use a "loose cannon" enzyme to set off an explosion of protein modifications inside infected bacteria.
Like all viruses, phages exist in a perpetual molecular arms race with their hosts. During nearly 4 billion years of coexistence, bacteria have evolved mechanisms to defend against infecting phages, while phages have evolved antidefense systems to shut down or evade these immune mechanisms. The new study demonstrates, for the first time, how a single phage protein can shut down multiple bacterial defenses with different mechanisms of action.
These findings resulted from a long-standing collaboration between two research groups at EMBL Heidelberg—the Typas Group, which specializes in systematic studies of bacterial interactions, and the Savitski Team, whose members are experts in cutting-edge proteomics technologies. "Phage research has led to a lot of exciting developments, including the CRISPR-Cas9 gene-editing system," said Mikhail Savitski, senior scientist, team leader and head of the Proteomics Core Facility at EMBL Heidelberg. "Using the sensitive technologies we had available in the lab, we wanted to understand in an unbiased way how phages affect bacterial proteins during infection." For this, they decided to use a well-known model system: E. coli, a rod-shaped bacterium that lives in our intestines, and T7 phage, a prototypical virus studied since the dawn of molecular biology that infects E. coli.
During infection, T7 uses the bacterium's own molecular machinery to create thousands of copies of itself, finally bursting out of the host cell and killing it in the process. The whole process typically takes 15 minutes. Given the speed of this infection process, the researchers decided to look more closely at post-translational protein modifications in infected bacteria.
Surprisingly, the scientists found that phage infection resulted in almost every bacterial protein becoming phosphorylated within minutes—at least in part of the protein pool in the cell. The likely culprit was T7 kinase, a phage enzyme first discovered in the 1970s. However, the scale and manner of phosphorylation were unlike anything previously observed.
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