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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • ADP Ribose Transferases / chemistry
  • ADP Ribose Transferases / genetics
  • ADP Ribose Transferases / metabolism*
  • ADP-Ribosylation
  • Adenosine Diphosphate / metabolism
  • Amino Acid Sequence
  • Bacterial Proteins / antagonists & inhibitors
  • Bacterial Proteins / metabolism*
  • Bacterial Toxins / chemistry
  • Bacterial Toxins / genetics
  • Bacterial Toxins / metabolism*
  • Catalytic Domain
  • Cytoskeletal Proteins / antagonists & inhibitors
  • Cytoskeletal Proteins / metabolism*
  • Escherichia coli / growth & development
  • Escherichia coli / immunology
  • Escherichia coli / metabolism
  • Humans
  • Mutagenesis, Site-Directed
  • N-Glycosyl Hydrolases / chemistry
  • N-Glycosyl Hydrolases / genetics
  • N-Glycosyl Hydrolases / metabolism*
  • Protein Structure, Tertiary
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Sequence Alignment
  • Serratia / metabolism
  • Time-Lapse Imaging

Substances

  • Bacterial Proteins
  • Bacterial Toxins
  • Cytoskeletal Proteins
  • FtsZ protein, Bacteria
  • Protein Subunits
  • Adenosine Diphosphate
  • ADP Ribose Transferases
  • N-Glycosyl Hydrolases
  • ADP-ribosylarginine hydrolase