Type II bacterial toxin–antitoxins: hypotheses, facts, and the newfound plethora of the PezAT system

Abstract

Toxin-antitoxin (TA) systems are entities found in the prokaryotic genomes, with eight reported types. Type II, the best characterised, is comprised of two genes organised as an operon. Whereas toxins impair growth, the cognate antitoxin neutralises its activity. TAs appeared to be involved in plasmid maintenance, persistence, virulence, and defence against bacteriophages. Most Type II toxins target the bacterial translational machinery. They seem to be antecessors of Higher Eukaryotes and Prokaryotes Nucleotide-binding (HEPN) RNases, minimal nucleotidyltransferase domains, or CRISPR-Cas systems. Four TAs encoded by Streptococcus pneumoniae, RelBE, YefMYoeB, Phd-Doc, and HicAB, belong to HEPN-RNases. The fifth is represented by PezAT/Epsilon-Zeta. PezT/Zeta toxins phosphorylate the peptidoglycan precursors, thereby blocking cell wall synthesis. We explore the body of knowledge (facts) and hypotheses procured for Type II TAs and analyse the data accumulated on the PezAT family. Bioinformatics analyses showed that homologues of PezT/Zeta toxin are abundantly distributed among 14 bacterial phyla mostly in Proteobacteria (48%), Firmicutes (27%), and Actinobacteria (18%), showing the widespread distribution of this TA. The pezAT locus was found to be mainly chromosomally encoded whereas its homologue, the tripartite omega-epsilon-zeta locus, was found mostly on plasmids. We found several orphan pezT/zeta toxins, unaccompanied by a cognate antitoxin.

Type II and IV toxin-antitoxin systems coordinately stabilize the integrative and conjugative element of the ICESa2603 family conferring multiple drug resistance in Streptococcus suis

“…Unexpectedly, the proteins DF184_04900-DF184_04905 encoded in the genetic neighborhood share sequence identities of 92% and 88.27% with the toxin AbiEii and antitoxin AbiEi, which constitute the type IV TA system AbiE in Streptococcus agalactiae [ 21 ]. Furthermore, DF184_04865 and DF184_05095, encoded by two non-contiguous genes, were identified as homologues of toxin zeta and antitoxin epsilon, respectively, which typically constitute a TA system in other bacteria [ 22 ]. These three TA systems are situated within the ICE Ssu HN105 [ 18 ], which harbors a variety of resistance genes ( Fig 1A ).…”