Phage proteins block and trigger retron toxin/antitoxin systems Institutional Repository Document uri icon

abstract

  • ABSTRACTBacteria carry dozens of Toxin/Antitoxin systems (TAs) in their chromosomes. Upon growth, the antitoxin is co-expressed and neutralizes the toxin. TAs can be activated and inhibit growth, but when and how this occurs has largely remained enigmatic, hindering our understanding of their physiological roles. We developed TIC/TAC (Toxin Inhibition/Activation Conjugation), a high-throughput reverse genetics approach, to systematically identify molecular blockers and triggers of TAs. By applying TIC/TAC to a tripartite TA, the retron-Sen2 ofSalmonellaTyphimurium, we have identified multiple blockers and triggers of phage origin. We demonstrate that diverse phage functionalities are sensed by the DNA-part of the antitoxin and ultimately activate the retron toxin. Phage-origin proteins can circumvent activation by directly blocking the toxin. Some identified triggers and blockers also act on anE. coliretron-TA, Eco9. We propose that retron-TAs act as abortive-infection anti-phage defense systems, and delineate mechanistic principles by which phages trigger or block them.

altmetric score

  • 71.05

author list (cited authors)

  • Bobonis, J., Mitosch, K., Mateus, A., Kritikos, G., Elfenbein, J. R., Savitski, M. M., Andrews-Polymenis, H., & Typas, A.

citation count

  • 23

complete list of authors

  • Bobonis, Jacob||Mitosch, Karin||Mateus, AndrĂ©||Kritikos, George||Elfenbein, Johanna R||Savitski, Mikhail M||Andrews-Polymenis, Helene||Typas, Athanasios

Book Title

  • bioRxiv

publication date

  • June 2020