International research team describes for the first time the structure and function of the Zorya system, a highly specialized antiviral protection mechanism against bacteria.
Bacteria are constantly infected by viruses, so-called phages, which use the bacteria as host cells. However, in the course of evolution, bacteria have developed a variety of strategies to protect themselves from these attacks. Many of these bacterial immunity systems have been known for a long time. Marc Erhardt and Philipp Popp, both from the Institute of Biology at Humboldt-Universität zu Berlin, together with colleagues in Denmark and New Zealand and other cooperation partners, have now deciphered the structure and function of a novel bacterial defense system against phages. It was originally discovered in 2018 by an Israeli research group and named after Zorya, a figure in Slavic mythology. The research results have now been published in the renowned journal Nature.
The Zorya system detects phage attacks and activates an early and precise defense that renders the virus harmless without the host cell dying. Zorya is like an early warning system with a protective shield. It recognizes the first signs of an attack and reacts with lightning speed to fend off the intruder," explains Marc Erhardt, head of the Molecular Microbiology research group at Humboldt University in Berlin and one of the lead authors of the study.
Molecular bulwark against phages
The investigation of the Zorya system using state-of-the-art methods such as cryo-electron and fluorescence microscopy shows that it consists of a unique molecular motor and several specialized components. This motor recognizes changes in the cell envelope caused by invading phages at an early stage and triggers a sequence of protective reactions. This previously unknown mechanism enables the bacterial cell to specifically degrade the phage DNA so that the virus cannot multiply in the host cell. This is remarkable, because bacteria usually prevent phages from multiplying by inducing cell death, i.e. "sacrificing" themselves. "Decoding the Zorya system was like opening a treasure chest," says Erhardt. "You keep discovering new facets of this molecular masterpiece."
To analyze the structure of the protein complexes, samples were cooled to very low temperatures down to -260 °C within fractions of a second using cryo-electron microscopy. This shock freezing prevents the formation of ice crystals so that molecules remain in their natural form. Fluorescence microscopy, in turn, provided an insight into the interaction of the virus particles with the bacterial cells.
New possibilities for biotechnological applications
The decoding of this virus defense system has far-reaching implications: On the one hand, it contributes to a better understanding of the mechanisms of phage-bacteria interaction. On the other hand, the findings open up new possibilities for biotechnological applications. The Zorya system could serve as a basis for the development of innovative tools for the targeted manipulation of genetic material or for the development of novel therapies against bacterial infections," adds Prof. Philipp Popp, visiting professor at the Institute of Biology and co-author of the study. The development of the Nobel Prize-winning CRISPR-Cas method for genome editing is also based on a bacterial immunity system discovered in the 2000s to protect against viruses. For Philipp Popp, this work is also an example of the beauty of molecular biology: "It is fascinating to see the elegant survival strategies that bacteria develop. Zorya shows us how much we can still learn about these tiny but incredibly complex organisms."
About the authors
Marc Erhardt heads the Molecular Microbiology group at the Institute of Biology at the Humboldt University of Berlin. His research focuses on the mechanisms of bacterial locomotion and phage defense systems. Philipp Popp is a visiting professor and group leader at the Institute of Biology at Humboldt-Universität. He conducts research at the interface of microscopy and molecular microbiology.
Photo: 3D model of the bacterial virus defense system Zorya
