@article{10902/30410, year = {2023}, url = {https://hdl.handle.net/10902/30410}, abstract = {Toxin-antitoxin (TA) systems are entities found in the prokaryotic genomes, with eight reported types. Type II, the best characterized, is comprised of two genes organized as an operon. Whereas toxins impair growth, the cognate antitoxin neutralizes 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. A total of 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.}, organization = {Funding. This research did not receive specific external funding. However, the laboratories of MPGB and of ME were supported by the Spanish Ministry of Science and Innovation, grants MCIN/AEI/10.13039/501100011033 PID2020-117923GB-I00, and PID2019-104553RB-C21, respectively. CCY was supported by the Malaysian Ministry of Higher Education grant FRGS/1/2019/SKK11/UNISZA/02/1. Acknowledgements. Thanks are due to friends and colleagues for never-ending scientific discussions. Apologies are also due to those colleagues that think they are under cited. We are thankful to Monica Fontenla for the improvements in the quality of the artwork and to Milagros Rodríguez Bueno for help with obtaining a waiver from CSIC. We also acknowledge the support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI), especially to Inmaculada Ramos Hita.}, publisher = {Oxford University Press}, publisher = {FEMS Microbiology Reviews}, title = {Type II bacterial toxin-antitoxins: hypotheses, facts, and the newfound plethora of the PezAT system}, author = {Chan, Wai Ting and Garcillán Barcia, María del Pilar and Yeo, Chew Chieng and Espinosa, Manuel}, }