Exploitation of eukaryotic ubiquitin signaling pathways by effectors translocated by bacterial type III and type IV secretion systems.
The specific and covalent addition of ubiquitin to proteins, known as ubiquitination, is a eukaryotic-specific modification central to many cellular processes, such as cell cycle progression, transcriptional regulation, and hormone signaling. Polyubiquitination is a signal for the 26S proteasome to destroy earmarked proteins, but depending on the polyubiquitin chain topology, it can also result in new protein properties. Both ubiquitin-orchestrated protein degradation and modification have also been shown to be essential for the host's immune response to pathogens. Many animal and plant pathogenic bacteria utilize type III and/or type IV secretion systems to inject effector proteins into host cells, where they subvert host signaling cascades as part of their infection strategy. Recent progress in the determination of effector function has taught us that playing with the host's ubiquitination system seems a general tactic among bacteria. Here, we discuss how bacteria exploit this system to control the timing of their effectors' action by programming them for degradation, to block specific intermediates in mammalian or plant innate immunity, or to target host proteins for degradation by mimicking specific ubiquitin/proteasome system components. In addition to analyzing the effectors that have been described in the literature, we screened publicly available bacterial genomes for mimicry of ubiquitin proteasome system subunits and detected several new putative effectors. Our understanding of the intimate interplay between pathogens and their host's ubiquitin proteasome system is just beginning. This exciting research field will aid in better understanding this interplay, and may also provide new insights into eukaryotic ubiquitination processes.
Angot
Aurélie
A
Laboratoire des Interactions Plantes Microorganismes, INRA/CNRS UMR 441/2594, BP52627, 31326 Castanet-Tolosan, France.
Vergunst
Annette
A
Genin
Stéphane
S
Peeters
Nemo
N
D000818:Animals; D001419:Bacteria / Q000378:metabolism / Q000472:pathogenicity*; D001425:Bacterial Outer Membrane Proteins / Q000502:physiology; D001426:Bacterial Proteins / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate; D008565:Membrane Proteins / Q000502:physiology; D021381:Protein Transport; D012486:Salmonella typhimurium / Q000472:pathogenicity; D015398:Signal Transduction / Q000502:physiology*; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000502:physiology
D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D008565:Membrane Proteins; C440638:SPI-2 protein, Salmonella; C419942:Spi1 protein, Salmonella; D025801:Ubiquitin; C111749:pseudomonas exoprotein A protein, Pseudomonas aeruginosa; C063239:yopE protein, Yersinia; D044767:Ubiquitin-Protein Ligases