Mode of action of a widespread Type IV toxin-antitoxin phage abortive infection resistance system.


Hannah Hampton, Simon Jackson, Anne Vogel, Ron Dy, Peter Fineran

University of Otago, Dunedin, New Zealand


Abortive infection (Abi) systems are one of many anti-phage systems used by bacteria to protect themselves from virus infection. Unlike other phage resistance strategies, Abi systems function at the expense of the infected bacterium, and thus are considered a form of “altruistic” cell suicide. Abi systems are normally dormant within the bacterial cell and become activated upon phage infection. Activated Abi systems then act upon cellular and/or phage targets, causing cellular growth inhibition and abortion of phage production. Over 20 Abis have been identified, yet the molecular basis for phage resistance of most is unknown. In 2009, an Abi system, ToxIN, from Pectobacterium atrosepticum was discovered and shown to function as a toxin-antitoxin (TA) system . TA systems are composed of a stable toxin and a more labile antitoxin. When the synthesis of both ceases, the antitoxin is preferentially degraded, enabling the more stable toxin to elicit its effects. The discovery of ToxIN, raised the question whether other Abis functioned in a similar manner. Our recent examination of lactococcal Abis led to the discovery of AbiE as a new family of TA modules. AbiE is widespread in many bacterial genomes with homologues found in a range of organisms, including the human pathogen Mycobacterium tuberculosis. AbiE is organized as a bicistronic operon and acts as a type IV toxin-antitoxin system (i.e. the toxin and antitoxin proteins do not interact). The toxin, AbiEii is a member of the DNA polβ superfamily of nucleotidyltransferases and causes toxicity by binding GTP and transferring this to an unknown target. The antitoxin, AbiEi, belongs to a family of putative transcriptional regulators and negatively autoregulates the abiE operon. AbiEi has a N-terminal DNA binding winged-helix-turn-helix (wHTH) domain essential for specific repression of abiE transcription. The uncharacterized C-terminal domain is made up of a novel fold that is sufficient for toxin neutralization in addition to being required for transcriptional repression.






Reference:
Posters Day 2-T03-Pos-40
Session:
Posters Covering Ecology, Host population control, Co-Evolutionary dynamics and Subversion/Evasion of Host Defences
Presenters:
Hannah Hampton
Session:
Day 2 Posters Covering: Ecology, Host population control, Co-evolutionary dynamics and Subversion/Evasion of host defences
Presentation type:
Poster presentation
Room:
Poster Halls
Date:
Tuesday, 19 July 2016
Time:
12:05 - 15:00