DNA Mimic Protein Ocr from Phage T7 Is a Potent Inhibitor of Brex Defence System

Bacteriophage Exclusion (BREX) is a phage defense system found in more than 10% of microbial genomes. In recent work we have shown that BREX from Escherichia coli HS provides protection against several unrelated DNA phages and discriminates between self and non-self by methylation of a specific DNA site. The mechanism of defensive action of BREX remains unclear, however. While T7 phage is able to productively infect BREX cells, we observed that a mutant phage without a functional 0.3 gene is subject to BREX exclusion. T7 gene 0.3 codes for the DNA mimic protein Ocr, a well-known inhibitor of type I restriction-modification systems. Expression of the 0.3 gene from a plasmid abolished BREX defense against T7 and other unrelated phages. Pull-down experiments demonstrated direct interaction of Ocr with BREX system methyltransferase BrxX. Yet, the DNA methylation level of cells harboring BREX system was not diminished in the presence of Ocr, suggesting that the inhibition of BREX defence occurs at a stage other than DNA methylation.

The study was supported by the RFBR grants â„–18-34-00845 mol_a and â„–19-34-90160.