Bacteriophage exclusion, a new defense system

Abstract

The ability to withstand viral predation is critical for survival of most microbes. Accordingly, a plethora of phage resistance systems has been identified in bacterial genomes (Labrie et al, 2010), including restriction‐modification systems (R‐M) (Tock & Dryden, 2005), abortive infection (Abi) (Chopin et al, 2005), Argonaute‐based interference (Swarts et al, 2014), as well as clustered regularly interspaced short palindromic repeats (CRISPR) and associated protein (Cas) adaptive immune system (CRISPR‐Cas) (Barrangou & Marraffini, 2014; Van der Oost et al, 2014). Predictably, the dark matter of bacterial genomes contains a wealth of genetic gold. A study published in this issue of The EMBO Journal by Goldfarb et al (2015) unveils bacteriophage exclusion (BREX) as a novel, widespread bacteriophage resistance system that provides innate immunity against virulent and temperate phage in bacteria.

Figure 1. Bacteriophage exclusion

(A) Invasion of a bacterial host by a temperate phage (left, red) and a lytic phage (purple, right). In the absence of an effective defense response, invasion will result in integration of the viral DNA in the host chromosome, whereas the DNA of the lytic viruses will be transcribed, translated and replicated, eventually leading to a new generation of viruses and lysis of the host cell. (B) Bacterial hosts that possess the bacteriophage exclusion (BREX) system are resistant to many (but not all) temperate and lytic phages. Different types of BREX systems are encoded by conserved gene clusters (in case of type-1 BREX from Bacillus cereus, two operons: brxABC-pglX and then pglZ-brxL). The well-conserved core of the BREX system includes three enzymes with (predicted) functionality: an ATP-binding P-loop protein (PglY/BrxC, C), an alkaline phosphatase (PglZ, Z) and a methyl-transferase (PglX, X) that specifically methylates TAGGAG. The B. cereusBREX system has been demonstrated to inhibit the integration of temperate phages, as well as the replication (and proliferation) of lytic phages (Goldfarb et al, 2015).