Listeria monocytogenes impairs SUMOylation for efficient infection

Nature. 2010 Apr 22;464(7292):1192-5. doi: 10.1038/nature08963.

Abstract

During infection, pathogenic bacteria manipulate the host cell in various ways to allow their own replication, propagation and escape from host immune responses. Post-translational modifications are unique mechanisms that allow cells to rapidly, locally and specifically modify activity or interactions of key proteins. Some of these modifications, including phosphorylation and ubiquitylation, can be induced by pathogens. However, the effects of pathogenic bacteria on SUMOylation, an essential post-translational modification in eukaryotic cells, remain largely unknown. Here we show that infection with Listeria monocytogenes leads to a decrease in the levels of cellular SUMO-conjugated proteins. This event is triggered by the bacterial virulence factor listeriolysin O (LLO), which induces a proteasome-independent degradation of Ubc9, an essential enzyme of the SUMOylation machinery, and a proteasome-dependent degradation of some SUMOylated proteins. The effect of LLO on Ubc9 is dependent on the pore-forming capacity of the toxin and is shared by other bacterial pore-forming toxins like perfringolysin O (PFO) and pneumolysin (PLY). Ubc9 degradation was also observed in vivo in infected mice. Furthermore, we show that SUMO overexpression impairs bacterial infection. Together, our results reveal that Listeria, and probably other pathogens, dampen the host response by decreasing the SUMOylation level of proteins critical for infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Toxins / metabolism
  • Cell Line
  • HeLa Cells
  • Heat-Shock Proteins / metabolism
  • Hemolysin Proteins / metabolism
  • Humans
  • Listeria monocytogenes / genetics
  • Listeria monocytogenes / metabolism
  • Listeria monocytogenes / pathogenicity*
  • Listeriosis / metabolism*
  • Listeriosis / microbiology*
  • Mice
  • Protein Processing, Post-Translational*
  • Small Ubiquitin-Related Modifier Proteins / genetics
  • Small Ubiquitin-Related Modifier Proteins / metabolism*
  • Ubiquitin-Conjugating Enzymes / metabolism
  • Virulence Factors / metabolism

Substances

  • Bacterial Toxins
  • Heat-Shock Proteins
  • Hemolysin Proteins
  • Small Ubiquitin-Related Modifier Proteins
  • Virulence Factors
  • Ubiquitin-Conjugating Enzymes
  • ubiquitin-conjugating enzyme UBC9
  • hlyA protein, Listeria monocytogenes