BREX

Contributors: Marian Dominguez-Mirazo

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 (, ) . BREX systems are found in around 10% of sequenced microbial genomes () .

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 () .

Molecular mechanism

B. cereus BREX Type 1 system was reported to methylate target motifs in the bacterial genome () . 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 ()

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 () .

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) (, ) .

Type 2 BREX systems include the system formerly known as Pgl, which is comprised of four genes (pglW, X, Y, and Z) () , to which () 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 () .

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

Among the 22,803 complete genomes of RefSeq, the BREX is detected in 1658 genomes (7.27 %).

The system was detected in 888 different species.

Proportion of genome encoding the BREX system for the 14 phyla with more than 50 genomes in the RefSeq database.

Structure

BREX_II

Example 1

BREX_III

Example 1

BREX_IV

Example 1

BREX_V

Example 1

BREX_VI

Example 1

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

    

References

10.1093/nar/gkaa290
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10.1093/nar/gky1125
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10.15252/embj.201489455
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