INFLUENCE OF THE PGLX PROTEIN MUTATIONS ON THE BREX PROTECTION

Justė Adomaitytė1, Tomas Šinkūnas1

1 Department of Protein – DNA Interactions, Institute of Biotechnology, Life Sciences Center, Vilnius

[email protected]

The ongoing co-evolution and co-adaptation of bacteria and bacteriophages has led to the development of antiviral defense systems that are encoded in regions of the bacterial genome called defense islands [1]. One of the bacterial antiviral defense systems is BREX (Bacteriophage Exclusion). It is present in about 10 % of prokaryotic genomes. This system inhibits bacteriophage replication by an unknown mechanism of action [2].

Type 1 BREX system consists of a cassette of 6 protein-coding genes: brxA, brxB, brxC, pglZ, brxL, pglX. The pglX gene encodes the m6A DNA methyltransferase, which methylates specific sequences in the host genome to distinguish itself from foreign DNA [2]. Bacteriophages can evade BREX protection by encoding protein inhibitors. The Ocr protein encoded by the T7 bacteriophage binds specifically to the PglX protein in a way that mimics the double-stranded helix of DNA and blocks BREX protection [3]. In this study, we analyse the influence of PglX mutations on BREX activity and its inhibition.


[1] K. S. Makarova, Y. I. Wolf, S. Snir, and E. V. Koonin, “Defense islands in bacterial and archaeal genomes and prediction of novel defense systems,” J Bacteriol, vol. 193, no. 21, pp. 6039–6056, Nov. 2011

[2] T. Goldfarb et al., “BREX is a novel phage resistance system widespread in microbial genomes,” EMBO J, vol. 34, no. 2, pp. 169–183, Jan. 2015

[3] A. Isaev et al., “Phage T7 DNA mimic protein Ocr is a potent inhibitor of BREX defence,” Nucleic Acids Res, vol. 48, no. 10, pp. 5397–5406, Jun. 2020