Bifunctional Immunity Proteins Protect Bacteria against FtsZ-Targeting ADP-Ribosylating Toxins

See Yeun Ting, Dustin E. Bosch, Sarah M. Mangiameli, Matthew C. Radey, Shuo Huang, Young Jun Park, Katherine A. Kelly, Szymon Krzysztof Filip, Young Ah Goo, Jimmy K. Eng, Marc Allaire, David Veesler, Paul A. Wiggins, S. Brook Peterson, Joseph D. Mougous*

*Corresponding author for this work

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

ADP-ribosylation of proteins can profoundly impact their function and serves as an effective mechanism by which bacterial toxins impair eukaryotic cell processes. Here, we report the discovery that bacteria also employ ADP-ribosylating toxins against each other during interspecies competition. We demonstrate that one such toxin from Serratia proteamaculans interrupts the division of competing cells by modifying the essential bacterial tubulin-like protein, FtsZ, adjacent to its protomer interface, blocking its capacity to polymerize. The structure of the toxin in complex with its immunity determinant revealed two distinct modes of inhibition: active site occlusion and enzymatic removal of ADP-ribose modifications. We show that each is sufficient to support toxin immunity; however, the latter additionally provides unprecedented broad protection against non-cognate ADP-ribosylating effectors. Our findings reveal how an interbacterial arms race has produced a unique solution for safeguarding the integrity of bacterial cell division machinery against inactivating post-translational modifications. A widely conserved toxin for interbacterial competition targets proteins for ADP-ribosylation, while antitoxins fight back using dual mechanisms of active site occlusion and enzymatic reversal of the modification, conferring broad immunity to diverse toxins.

Original languageEnglish (US)
Pages (from-to)1380-1392.e14
JournalCell
Volume175
Issue number5
DOIs
StatePublished - Nov 15 2018

Keywords

  • ADP-ribosylation
  • Esx secretion
  • bacterial communities
  • toxin
  • type VI secretion

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Ting, S. Y., Bosch, D. E., Mangiameli, S. M., Radey, M. C., Huang, S., Park, Y. J., Kelly, K. A., Filip, S. K., Goo, Y. A., Eng, J. K., Allaire, M., Veesler, D., Wiggins, P. A., Peterson, S. B., & Mougous, J. D. (2018). Bifunctional Immunity Proteins Protect Bacteria against FtsZ-Targeting ADP-Ribosylating Toxins. Cell, 175(5), 1380-1392.e14. https://doi.org/10.1016/j.cell.2018.09.037