The bacterial Type III toxin-antitoxin system, ToxIN, is a dynamic protein-RNA complex with stability-dependent antiviral abortive infection activity.
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Short, F., Akusobi, C., Broadhurst, B., & Salmond, G. (2018). The bacterial Type III toxin-antitoxin system, ToxIN, is a dynamic protein-RNA complex with stability-dependent antiviral abortive infection activity.. Scientific reports, 8 (1), 1013. https://doi.org/10.1038/s41598-017-18696-x
Bacteria have evolved numerous defense systems to protect themselves from viral (bacteriophage) infection. The ToxIN system of Pectobacterium atrosepticum is a Type III toxin-antitoxin complex and “altruistic suicide” anti-phage system, which kills phage-infected cells through the release of a ribonuclease toxin, ToxN. ToxN is counteracted by a co-transcribed antitoxic RNA pseudoknot, ToxI, which self-assembles with ToxN into an inactive 3ToxI:3ToxN complex in vitro. However it is not known whether this complex is predominant in vivo, or how the complex is disassembled following infection to trigger a lethal, “altruistic” response. In this study, we characterise ToxI turnover and folding, and explore the link between complex stability and anti-phage activity, with a view to understanding events that lead to ToxN-mediated suicide following phage infection. We present evidence that ToxN constantly cleaves fresh ToxI in vivo rather than staying associated with pre-processed antitoxin, and that the ToxI antitoxin can partially fold spontaneously using conserved nucleotides. We also show that reducing the stability of the ToxIN complex can increase the strength of the antiviral response in a phage-dependent manner. Based on this information, we propose a revised model for ToxN inhibition, complex assembly and activation by infecting bacteriophage.
Pectobacterium, Bacteriophages, Ribonucleases, Bacterial Proteins, RNA, Bacterial, Antitoxins, Transcription, Genetic, Gene Expression Regulation, Bacterial, Nucleic Acid Conformation, Base Pairing, Protein Binding, Protein Folding, Protein Stability, Toxin-Antitoxin Systems
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External DOI: https://doi.org/10.1038/s41598-017-18696-x
This record's URL: https://www.repository.cam.ac.uk/handle/1810/273507
Attribution 4.0 International
Licence URL: http://creativecommons.org/licenses/by/4.0/
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