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Cell. 2018 Nov 15;175(5):1380-1392.e14. doi: 10.1016/j.cell.2018.09.037. Epub 2018 Oct 18.

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

Author information

1
Department of Microbiology, University of Washington School of Medicine, Seattle, WA 98195, USA.
2
Department of Pathology, University of Washington School of Medicine, Seattle, WA 98195, USA.
3
Department of Physics, University of Washington, Seattle, WA 98195, USA.
4
Department of Biochemistry, University of Washington School of Medicine, Seattle, WA 98195, USA.
5
Proteomics Center of Excellence, Northwestern University, Chicago, IL 60611, USA.
6
Proteomics Resource, University of Washington, Seattle, WA 98195, USA.
7
Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
8
Department of Microbiology, University of Washington School of Medicine, Seattle, WA 98195, USA; Department of Physics, University of Washington, Seattle, WA 98195, USA; Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.
9
Department of Microbiology, University of Washington School of Medicine, Seattle, WA 98195, USA; Department of Biochemistry, University of Washington School of Medicine, Seattle, WA 98195, USA; Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA. Electronic address: mougous@uw.edu.

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.

KEYWORDS:

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

PMID:
30343895
PMCID:
PMC6239978
[Available on 2019-11-15]
DOI:
10.1016/j.cell.2018.09.037

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