AbiEi Binds Cooperatively to the Type IV abiE Toxin-Antitoxin Operator Via a Positively-Charged Surface and Causes DNA Bending and Negative Autoregulation

J Mol Biol. 2018 Apr 13;430(8):1141-1156. doi: 10.1016/j.jmb.2018.02.022. Epub 2018 Mar 6.


Bacteria resist phage infection using multiple strategies, including CRISPR-Cas and abortive infection (Abi) systems. Abi systems provide population-level protection from phage predation, via "altruistic" cell suicide. It has recently been shown that some Abi systems function via a toxin-antitoxin mechanism, such as the widespread AbiE family. The Streptococcus agalactiae AbiE system consists of a bicistronic operon encoding the AbiEi antitoxin and AbiEii toxin, which function as a Type IV toxin-antitoxin system. Here we examine the AbiEi antitoxin, which belongs to a large family of transcriptional regulators with a conserved N-terminal winged helix-turn-helix domain. This winged helix-turn-helix is essential for transcriptional repression of the abiE operon. The function of the AbiEi C-terminal domain is poorly characterized, but it contributes to transcriptional repression and is sufficient for toxin neutralization. We demonstrate that a conserved charged surface on one face of the C-terminal domain assists sequence-specific DNA binding and negative autoregulation, without influencing antitoxicity. Furthermore, AbiEi binds cooperatively to two inverted repeats within the abiE promoter and bends the DNA by 72°. These findings demonstrate that the mechanism of DNA binding by the widespread family of AbiEi antitoxins and transcriptional regulators can contribute to negative autoregulation.

Keywords: AbiE; COG5340; abortive infection system; phage resistance; toxin–antitoxin system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitoxins / chemistry
  • Antitoxins / metabolism
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism
  • Bacterial Toxins / genetics*
  • Bacterial Toxins / metabolism
  • Gene Expression Regulation, Bacterial
  • Models, Molecular
  • Multigene Family
  • Operon
  • Promoter Regions, Genetic
  • Protein Conformation
  • Protein Domains
  • Streptococcus anginosus / chemistry
  • Streptococcus anginosus / genetics
  • Streptococcus anginosus / metabolism*
  • Transcription Factors / chemistry*
  • Transcription Factors / metabolism*


  • Antitoxins
  • Bacterial Proteins
  • Bacterial Toxins
  • Transcription Factors