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Biology and evolution of bacterial toxin–antitoxin systems

Abstract

Toxin–antitoxin systems are widespread in bacterial genomes. They are usually composed of two elements: a toxin that inhibits an essential cellular process and an antitoxin that counteracts its cognate toxin. In the past decade, a number of new toxin–antitoxin systems have been described, bringing new growth inhibition mechanisms to light as well as novel modes of antitoxicity. However, recent advances in the field profoundly questioned the role of these systems in bacterial physiology, stress response and antimicrobial persistence. This shifted the paradigm of the functions of toxin–antitoxin systems to roles related to interactions between hosts and their mobile genetic elements, such as viral defence or plasmid stability. In this Review, we summarize the recent progress in understanding the biology and evolution of these small genetic elements, and discuss how genomic conflicts could shape the diversification of toxin–antitoxin systems.

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Fig. 1: Currently proposed types of toxin–antitoxin system.
Fig. 2: Major types of regulation of toxin–antitoxin systems.
Fig. 3: Cellular activities of toxins of toxin–antitoxin systems.
Fig. 4: Roles of toxin–antitoxin systems in genomic conflicts.
Fig. 5: Comparison of chromosomes and toxin–antitoxin locus between Escherichia coli strains.

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Acknowledgements

Work in the L.V.M. laboratory is funded by the Wallonia Region (Algotech, grant 1510598), the ARC actions 2018–2023 and the FNRS-FRS (CDR ‘PERSIST’, grant J010818F). D.J. is supported by an FRM postdoctoral fellowship (SPF201809007142).

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Glossary

Inteins

Internal segments of proteins that self-excise and ligate the remaining segments (exteins) during protein splicing.

Chaperone-addiction motifs

Specific sequences that promote antitoxin destabilization unless recognized by the chaperone.

DNA gyrase

Type II topoisomerase enzyme that relieves positive supercoiling in front of the replication forks.

Aminoacylation

Ligation of an amino acid to its cognate tRNA, also known as tRNA charging.

AMPylase

Enzyme that ligates AMP to an amino acid side chain of a target protein.

Thymineless death

Rapid loss of viability occurring as a result of thymine deprivation.

Anti-Shine–Dalgarno sequence

Sequence in the prokaryotic ribosome that helps to align the ribosome for translation initiation at the ATG start codon.

Iteron sequences

DNA sequences recognized by replication initiation proteins that are involved in the control of the copy number of plasmids.

Genetic drift

Stochastic fluctuations in the frequency of alleles that occur randomly and can eventually lead to the loss or fixation of these alleles.

Phylogroups

Taxonomic groups of organisms related through their evolutionary history.

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Jurėnas, D., Fraikin, N., Goormaghtigh, F. et al. Biology and evolution of bacterial toxin–antitoxin systems. Nat Rev Microbiol 20, 335–350 (2022). https://doi.org/10.1038/s41579-021-00661-1

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