BREX

Description

BREX (for Bacteriophage Exclusion) is a family of anti-phage defense systems. BREX systems are active against both lytic and lysogenic phages. They allow phage adsorption but block phage DNA replication, and are considered to be RM-like systems (N/A, N/A) . BREX systems are found in around 10% of sequenced microbial genomes (N/A) .

BREX systems can be divided into six subtypes, and are encoded by 4 to 8 genes, some of these genes being mandatory while others are subtype-specific (N/A) .

Molecular mechanism

B. cereus BREX Type 1 system was reported to methylate target motifs in the bacterial genome (N/A) . The methylation activity of this system has been hypothesized to allow for self from non-self discrimination, as it is the case for Restriction-Modification (RM) systems. 

However, the mechanism through which BREX Type 1 systems defend against phages is distinct from RM systems, and does not seem to degrade phage nucleic acids (N/A) . 

To date, BREX molecular mechanism remains to be described.

Example of genomic structure

BREX systems necessarily include the pglZ gene (encoding for a putative alkaline phosphatase), which is accompanied by either brxC or pglY. These two genes share only a distant homology but have been hypothesized to fulfill the same function among the different BREX subtypes (N/A) .

Goldfarb and colleagues reported a 6-gene cassette from Bacillus cereus as being the model for BREX Type 1. BREX Type 1 are the most widespread BREX systems, and present two core genes (pglZ and brxC).  Four other genes  are associated with BREX Type 1 : *pglX (*encoding for a putative methyltransferase),  *brxA (encoding an RNA-binding anti-termination protein), brxB (unknown function), brxC (*encoding for a protein with ATP-binding domain) and brxL (encoding for a putative protease) (N/A, N/A) .

Type 2 BREX systems include the system formerly known as Pgl, which is comprised of four genes (pglW, X, Y, and Z) (N/A) , to which (N/A) found often associated two additional genes (brxD, and brxHI).

Although 4 additional BREX subtypes have been proposed, BREX Type 1 and Type 2 remain the only ones to be experimentally validated. A detailed description of the other subtypes can be found in (N/A) .

A total of 6 subsystems have been described for the BREX system.

Here is some examples found in the RefSeq database:

The BREX_I system in Mycobacterium kubicae (GCF_015689175.1, NZ_CP065047) is composed of 6 proteins brxA_DUF1819 (WP_241007777.1) brxB_DUF1788 (WP_174814228.1) brxC (WP_085074024.1) pglX1 (WP_085074003.1) pglZA (WP_085074004.1) brxL (WP_085074005.1)

The BREX_II system in Nocardia terpenica (GCF_002568625.1, NZ_CP023778) is composed of 6 proteins pglW (WP_232535326.1) pglX2 (WP_098693854.1) pglY (WP_098693855.1) pglZ2 (WP_098693856.1) brxD (WP_098693857.1) brxHI (WP_098693858.1)

The BREX_III system in Rubinisphaera brasiliensis (GCF_000165715.2, NC_015174) is composed of 5 proteins pglZ3 (WP_013627487.1) brxHII (WP_013627488.1) pglXI (WP_013627489.1) brxC (WP_041397812.1) brxF (WP_218916504.1)

The BREX_IV system in Olsenella sp. oral taxon 807 (GCF_001189515.2, NZ_CP012069) is composed of 4 proteins brxL (WP_050344523.1) pglZ4 (WP_172674480.1) brxC4 (WP_050340978.1) brxP (WP_050340980.1)

The BREX_V system in Heyndrickxia vini (GCF_016772275.1, NZ_CP065425) is composed of 7 proteins brxHII (WP_202780866.1) pglZA (WP_202778092.1) pglX1 (WP_202778093.1) pglX1 (WP_202778094.1) brxC (WP_202778095.1) brxB_DUF1788 (WP_246483846.1) brxA_DUF1819 (WP_202778096.1)

The BREX_VI system in Virgibacillus halodenitrificans (GCF_001878675.1, NZ_CP017962) is composed of 8 proteins brxE (WP_071648637.1) brxA_DUF1819 (WP_071648638.1) brxB_DUF1788 (WP_071648639.1) brxC (WP_197035844.1) pglX1 (WP_071648641.1) pglZA (WP_071648642.1) brxD (WP_071648643.1) brxHI (WP_071648644.1)

Distribution of the system among prokaryotes

Structure

Experimental validation

      
graph LR;
    Gao_2020[Gao et al., 2020] --> Origin_0
    Gordeeva_2017[Gordeeva et al., 2019] --> Origin_0
    Origin_0[Escherichia coli 
WP_085962535.1, WP_000566901.1,
WP_001019648.1, WP_021524842.1,
WP_001180895.1, WP_001193074.1] --> Expressed_0[Escherichia coli]
    Expressed_0[Escherichia coli] ----> Lambda
    Goldfarb_2015[Goldfarb et al., 2015] --> Origin_1
    Origin_1[Bacillus cereus 
ZP_02596040.1, ZP_02596039.1,
ZP_02596038.1, ZP_02596037.1,
ZP_02596036.1, ZP_02596035.1] --> Expressed_1[Bacillus subtilis ]
    Expressed_1[Bacillus subtilis ] ----> SPbeta & SP16 & Zeta & phi3T & SPO2 & SPO1 & SP82G
    subgraph Title1[Reference]
        Gao_2020
        Gordeeva_2017
        Goldfarb_2015
end
    subgraph Title2[System origin]
        Origin_0
        Origin_0
        Origin_1
end
    subgraph Title3[Expression species]
        Expressed_0
        Expressed_0
        Expressed_1
end
    subgraph Title4[Protects against]
        Lambda
        Lambda
        SPbeta
        SP16
        Zeta
        phi3T
        SPO2
        SPO1
        SP82G
end
    style Title1 fill:none,stroke:none,stroke-width:none
    style Title2 fill:none,stroke:none,stroke-width:none
    style Title3 fill:none,stroke:none,stroke-width:none
    style Title4 fill:none,stroke:none,stroke-width:none