A widespread bacteriophage abortive infection system functions through a Type IV toxin–antitoxin mechanism

Abstract

Bacterial abortive infection (Abi) systems are ‘altruistic’ cell death systems that are activated by phage infection and limit viral replication, thereby providing protection to the bacterial population. Here, we have used a novel approach of screening Abi systems as a tool to identify and characterize toxin–antitoxin (TA)-acting Abi systems. We show that AbiE systems are encoded by bicistronic operons and function via a non-interacting (Type IV) bacteriostatic TA mechanism. The abiE operon was negatively autoregulated by the antitoxin, AbiEi, a member of a widespread family of putative transcriptional regulators. AbiEi has an N-terminal winged-helix-turn-helix domain that is required for repression of abiE transcription, and an uncharacterized bi-functional C-terminal domain, which is necessary for transcriptional repression and sufficient for toxin neutralization. The cognate toxin, AbiEii, is a predicted nucleotidyltransferase (NTase) and member of the DNA polymerase β family. AbiEii specifically bound GTP, and mutations in conserved NTase motifs (I-III) and a newly identified motif (IV), abolished GTP binding and subsequent toxicity. The AbiE systems can provide phage resistance and enable stabilization of mobile genetic elements, such as plasmids. Our study reveals molecular insights into the regulation and function of the widespread bi-functional AbiE Abi-TA systems and the biochemical properties of both toxin and antitoxin proteins.

Evolutionary Ecology of Prokaryotic Immune Mechanisms

“…To date, over 23 lactococcal Abi systems have been identified, all of which are thought to interfere with different steps of the phage replication cycle (1,101). Recent studies have shown that certain toxin-antitoxin (TA) systems can also act as Abi systems upon activation by phage infection (104)(105)(106). For example, the plant-pathogenic bacterium Pectobacterium atrosepticum encodes the TA system ToxIN, which aborts phage infection.…”

The Native Plasmid pML21 Plays a Role in Stress Tolerance in Enterococcus faecalis ML21, as Analyzed by Plasmid Curing Using Plasmid Incompatibility

“…The results suggest that orf5 of pML21 may play a major role in stress tolerance in E. faecalis ML21, although the role of TA system in bacterial stress response are still remain debate [29,30]. Actually, recent reports indicated some bacterial abortive infection systems also function through TA mechanism [31,32]; this may be a explanation for the stress hypersensitivity of E. faecalis ML0 expressing orf3 and orf4. Interestingly, E. faecalis ML0-harboring pML23e showed significantly higher survival compared to other strains (Fig.…”

Modulation of Bacterial Proliferation as a Survival Strategy

“…In C. crescentus, the toxin SocB interferes with DnaN and thereby blocks the process of DNA replication (Aakre, Phung, Huang, & Laub, 2013). It has been proposed that TA systems benefit bacteria at a population level, for example, by inducing cell death or bacteriostasis in response to phage infection, thereby thwarting phage replication (Dy, Przybilski, Semeijn, Salmond, & Fineran, 2014). It has also been suggested that TA-induced suicide in response to nutrient starvation would set nutrients free to ensure the survival of the remaining cells.…”