ZORYA – A NOVEL DEFENSE SYSTEM WIDESPREAD IN BACTERIA, WITH A BROAD ANTI-PHAGE ACTIVITY

Anna Lopatina Azita Leavitt Sarah Melamed Gal Ofir Gil Amitai Rotem Sorek
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel

The perpetual arms race between phages and bacteria is driving the innovative evolution of multiple, sophisticated defense strategies in prokaryotes that can be adapted to invaluable molecular biology tools such as restriction enzymes and CRISPR-Cas9. Recently, in a massive study performed in our lab, 10 previously unknown defense mechanisms of bacteria have been revealed, doubling the amount of prokaryotic immune systems known today. One of the systems of special interest, named Zorya, seemed to “borrow” two of its four genes from non-defensive bacterial systems. Particularly, its mechanism of immunity contains homologs of components of a proton channel that is also used in the motors of bacterial flagella. These domains had never been identified before as being involved in defense.

In our studies, Zorya showed strong protection against a broad range of phages, including several morphological families of dsDNA and ssDNA phages, pointing to a high degree of flexible molecular specificity. All four genes in the system appear to be essential for its functionality, as deletion of each of the genes resulted in a loss of protection from phage infection. Moreover, point mutations in the active centers of two genes forming a proton translocation channel yielded a nonfunctional system. Further experiments showed that Zorya is a conditional abortive infection system. The details of the defense mechanism of Zorya system will be further discussed.









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