TY - JOUR
T1 - Phage T7 DNA mimic protein Ocr is a potent inhibitor of BREX defence
AU - Isaev, Artem
AU - Drobiazko, Alena
AU - Sierro, Nicolas
AU - Gordeeva, Julia
AU - Yosef, Ido
AU - Qimron, Udi
AU - Ivanov, Nikolai V.
AU - Severinov, Konstantin
N1 - Publisher Copyright:
© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - BREX (for BacteRiophage EXclusion) is a superfamily of common bacterial and archaeal defence systems active against diverse bacteriophages. While the mechanism of BREX defence is currently unknown, self versus non-self differentiation requires methylation of specific asymmetric sites in host DNA by BrxX (PglX) methyltransferase. Here, we report that T7 bacteriophage Ocr, a DNA mimic protein that protects the phage from the defensive action of type I restriction–modification systems, is also active against BREX. In contrast to the wild–type phage, which is resistant to BREX defence, T7 lacking Ocr is strongly inhibited by BREX, and its ability to overcome the defence could be complemented by Ocr provided in trans. We further show that Ocr physically associates with BrxX methyltransferase. Although BREX+ cells overproducing Ocr have partially methylated BREX sites, their viability is unaffected. The result suggests that, similar to its action against type I R–M systems, Ocr associates with as yet unidentified BREX system complexes containing BrxX and neutralizes their ability to both methylate and exclude incoming phage DNA.
AB - BREX (for BacteRiophage EXclusion) is a superfamily of common bacterial and archaeal defence systems active against diverse bacteriophages. While the mechanism of BREX defence is currently unknown, self versus non-self differentiation requires methylation of specific asymmetric sites in host DNA by BrxX (PglX) methyltransferase. Here, we report that T7 bacteriophage Ocr, a DNA mimic protein that protects the phage from the defensive action of type I restriction–modification systems, is also active against BREX. In contrast to the wild–type phage, which is resistant to BREX defence, T7 lacking Ocr is strongly inhibited by BREX, and its ability to overcome the defence could be complemented by Ocr provided in trans. We further show that Ocr physically associates with BrxX methyltransferase. Although BREX+ cells overproducing Ocr have partially methylated BREX sites, their viability is unaffected. The result suggests that, similar to its action against type I R–M systems, Ocr associates with as yet unidentified BREX system complexes containing BrxX and neutralizes their ability to both methylate and exclude incoming phage DNA.
UR - http://www.scopus.com/inward/record.url?scp=85085904765&partnerID=8YFLogxK
U2 - 10.1093/NAR/GKAA290
DO - 10.1093/NAR/GKAA290
M3 - Article
C2 - 32338761
AN - SCOPUS:85085904765
SN - 0305-1048
VL - 48
SP - 5397
EP - 5406
JO - Nucleic Acids Research
JF - Nucleic Acids Research
IS - 10
ER -