BREX – A NOVEL ANTI-PHAGE DEFENSE SYSTEM IN BACTERIA

Tamara Goldfarb Hila Sberro Eyal Weinstock Ofir Cohen Shany Doron Yoav Charpak Amikam Shaked Afik Gal Ofir Rotem Sorek
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot

The perpetual arms race between bacteria and phage has resulted in the evolution of efficient resistance systems that protect bacteria from phage infection. Such systems, which include the CRISPR-Cas and restriction-modification systems, have proven to be invaluable in the biotechnology and dairy industries. By studying genes that are enriched in “Defense Islands”1 in bacterial and archaeal genomes, we have identified a 6 genes system, which is prevalent in ~10% of the sequenced genomes. This novel system was denoted Bacteriophage Exclusion (BREX)2. To verify its function as a defense system, the BREX cassette of Bacillus cereus was transferred into the genome of Bacillus subtilis, which naturally lacks a native BREX system. The transformed B. subtilis became resistant to several Bacillus phages, both temperate and lytic ones. Further experiments have shown that BREX does not prevent the adsorption of phages, but eliminates lysogeny and phage DNA replication. BREX causes the methylation of a non-palindromic site, TAGGAG, in the bacterial genome, and the BREX methylase is an essential component for BREX protection. We are currently working on deciphering BREX mechanism of defense by both genomic and biochemical approaches.

  1. Makarova, K. S., Wolf, Y. I., Snir, S. & Koonin, E. V. Defense islands in bacterial and archaeal genomes and prediction of novel defense systems. J. Bacteriol. 193, 6039–56 (2011).
  2. Goldfarb, T., Sberro, H., Weinstock, E., Cohen, O., Doron, S., Charpak Amikam, Y., Afik, S., Ofir, G., Sorek, R., BREX is a novel phage resistance system widespread in microbial genomes. EMBO J. e201489455 (2014). doi:10.15252/embj.201489455








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