Structure, Evolution, and Functions of Bacterial Type III Toxin-Antitoxin Systems

Abstract

Toxin-antitoxin (TA) systems are small genetic modules that encode a toxin (that targets an essential cellular process) and an antitoxin that neutralises or suppresses the deleterious effect of the toxin. Based on the molecular nature of the toxin and antitoxin components, TA systems are categorised into different types. Type III TA systems, the focus of this review, are composed of a toxic endoribonuclease neutralised by a non-coding RNA antitoxin in a pseudoknotted configuration. Bioinformatic analysis shows that the Type III systems can be classified into subtypes. These TA systems were originally discovered through a phage resistance phenotype arising due to a process akin to an altruistic suicide; the phenomenon of abortive infection. Some Type III TA systems are bifunctional and can stabilise plasmids during vegetative growth and sporulation. Features particular to Type III systems are explored here, emphasising some of the characteristics of the RNA antitoxin and how these may affect the co-evolutionary relationship between toxins and cognate antitoxins in their quaternary structures. Finally, an updated analysis of the distribution and diversity of these systems are presented and discussed.

Nitrosomonas europaea MazF Specifically Recognises the UGG Motif and Promotes Selective RNA Degradation

“…Currently, these systems are grouped into six distinct classes depending on antitoxin features ( Page and Peti, 2016 ; Hall et al, 2017 ). In type I and type III, the antitoxins comprise RNAs that mask toxin activities by repressing toxin translation or directly binding to corresponding toxins, respectively ( Brantl, 2012 ; Goeders et al, 2016 ). In other TA systems, the antitoxins consist of proteins that counteract the toxins by forming a TA protein complex (type II) ( Gerdes et al, 2005 ), functioning as an antagonist of the toxin (type IV) ( Masuda et al, 2012a , b ), inhibiting translation by destabilising the toxin mRNA (type V) ( Wang et al, 2012 ), or serving as an adaptor molecule to introduce the toxin to cellular protease (type VI) ( Aakre et al, 2013 ).…”

Adaptive suicide: is a kin-selected driver of fatal behaviours likely?

“…Beyond sensing population levels by quorum-sensing, proteins that can sense damage and 'predict' the outcome of infections will also be important in mediating Abi systems and toxin -antitoxins [65,66] that colocalize with immunity genes [57]. The exact mechanisms and structures that forecast the course of virus infections remain to be fully elucidated, but it is thought that whenever dedicated sensor molecules indicate an attack is manageable the cell mobilizes its immune system, while if the indications of attack are dire then self-afflicting programmes are triggered [57].…”

Toxin–antitoxin systems and their role in disseminating and maintaining antimicrobial resistance

“…For example, toxIN Bt located on pAW63 from Bacillus thuringiensis encodes a toxic protein ToxN Bt and a antitoxin ToxI Bt containing 2.9 tandem repeats of a 34-nucleotide sequence (Short, Monson and Salmond 2015 ; Goeders et al . 2016 ). Currently, type III TAs are divided into three subgroups sharing the same genetic organisation, namely toxIN , cptIN (for Coprococcus type III inhibitor-toxiN) and tenpIN (for type III ENdogenous to Photorhabdus inhibitor-toxiN) (Blower et al .…”

“… 2012 ; Goeders et al . 2016 ). Though these subgroups were identified by shared identity with ToxN, their cognates diverge between and within the subtypes, such as the number of repeats and the length of repeats (Blower et al .…”