1887

Abstract

In the complete genome sequences of NCTC9343 and 638R, we have discovered a gene, the product of which has 63 % identity to human ubiquitin and cross-reacts with antibodies raised against bovine ubiquitin. The sequence of is closest in identity (76 %) to the ubiquitin gene from a migratory grasshopper entomopoxvirus, suggesting acquisition by inter-kingdom horizontal gene transfer. We have screened clinical isolates of from diverse geographical regions and found that is present in some, but not all, strains. The gene is transcribed and the mRNA is translated in , but deletion of did not have a detrimental effect on growth. BfUbb has a predicted signal sequence; both full-length and processed forms were detected in whole-cell extracts, while the processed form was found in concentrated culture supernatants. Purified recombinant BfUbb inhibited ubiquitination and was able to covalently bind the human E1 activating enzyme, suggesting it could act as a suicide substrate . is one of the predominant members of the normal human gastrointestinal microbiota with estimates of up to >10 cells per g faeces by culture. These data indicate that the gastro-intestinal tract of some individuals could contain a significant amount of aberrant ubiquitin with the potential to inappropriately activate the host immune system and/or interfere with eukaryotic ubiquitin activity. This discovery could have profound implications in relation to our understanding of human diseases such as inflammatory bowel and autoimmune diseases.

Funding
This study was supported by the:
  • Biotechnology and Biological Sciences Research Council (BBSRC)
  • Department of Employment and Learning Northern Ireland
  • BBSRC (Award BB-C505875-1)
  • Wellcome Trust (Award WT090288MA)
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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2011-11-01
2024-11-13
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References

  1. Bhoj V. G., Chen Z. J. ( 2009). Ubiquitylation in innate and adaptive immunity. Nature 458:430–437 [View Article][PubMed]
    [Google Scholar]
  2. Bomberger J. M., Maceachran D. P., Coutermarsh B. A., Ye S., O’Toole G. A., Stanton B. A. ( 2009). Long-distance delivery of bacterial virulence factors by Pseudomonas aeruginosa outer membrane vesicles. PLoS Pathog 5:e1000382 [View Article][PubMed]
    [Google Scholar]
  3. Boyer L., Lemichez E. ( 2004). Targeting of host-cell ubiquitin and ubiquitin-like pathways by bacterial factors. Nat Rev Microbiol 2:779–788 [View Article][PubMed]
    [Google Scholar]
  4. Cadwell K., Coscoy L. ( 2005). Ubiquitination on nonlysine residues by a viral E3 ubiquitin ligase. Science 309:127–130 [View Article][PubMed]
    [Google Scholar]
  5. Carver T., Berriman M., Tivey A., Patel C., Böhme U., Barrell B. G., Parkhill J., Rajandream M. A. ( 2008). Artemis and ACT: viewing, annotating and comparing sequences stored in a relational database. Bioinformatics 24:2672–2676 [View Article][PubMed]
    [Google Scholar]
  6. Cerdeño-Tárraga A. M., Patrick S., Crossman L. C., Blakely G., Abratt V., Lennard N., Poxton I., Duerden B., Harris B. et al. & other authors ( 2005). Extensive DNA inversions in the B. fragilis genome control variable gene expression. Science 307:1463–1465 [View Article][PubMed]
    [Google Scholar]
  7. Cheng C. W., Lin H. S., Ye J. J., Yang C. C., Chiang P. C., Wu T. S., Lee M. H. ( 2009). Clinical significance of and outcomes for Bacteroides fragilis bacteremia. J Microbiol Immunol Infect 42:243–250 [View Article][PubMed]
    [Google Scholar]
  8. Erbse A., Schmidt R., Bornemann T., Schneider-Mergener J., Mogk A., Zahn R., Dougan D. A., Bukau B. ( 2006). ClpS is an essential component of the N-end rule pathway in Escherichia coli. Nature 439:753–756 [View Article][PubMed]
    [Google Scholar]
  9. Fletcher C. M., Coyne M. J., Comstock L. E. ( 2011). Theoretical and experimental characterization of the scope of protein O-glycosylation in Bacteroides fragilis. J Biol Chem 286:3219–3226 [View Article][PubMed]
    [Google Scholar]
  10. Gottesman S., Roche E., Zhou Y., Sauer R. T. ( 1998). The ClpXP and ClpAP proteases degrade proteins with carboxy-terminal peptide tails added by the SsrA-tagging system. Genes Dev 12:1338–1347 [View Article][PubMed]
    [Google Scholar]
  11. Hochstrasser M. ( 2009). Origin and function of ubiquitin-like proteins. Nature 458:422–429 [View Article][PubMed]
    [Google Scholar]
  12. Karin M., Ben-Neriah Y. ( 2000). Phosphorylation meets ubiquitination: the control of NF-κB activity. Annu Rev Immunol 18:621–663 [View Article][PubMed]
    [Google Scholar]
  13. Komander D. ( 2009). The emerging complexity of protein ubiquitination. Biochem Soc Trans 37:937–953 [View Article][PubMed]
    [Google Scholar]
  14. Komatsu M., Ichimura Y. ( 2010). Selective autophagy regulates various cellular functions. Genes Cells 15:923–933 [View Article][PubMed]
    [Google Scholar]
  15. Kuehn M. J., Kesty N. C. ( 2005). Bacterial outer membrane vesicles and the host–pathogen interaction. Genes Dev 19:2645–2655 [View Article][PubMed]
    [Google Scholar]
  16. Kuwahara T., Yamashita A., Hirakawa H., Nakayama H., Toh H., Okada N., Kuhara S., Hattori M., Hayashi T., Ohnishi Y. ( 2004). Genomic analysis of Bacteroides fragilis reveals extensive DNA inversions regulating cell surface adaptation. Proc Natl Acad Sci U S A 101:14919–14924 [View Article][PubMed]
    [Google Scholar]
  17. Le Negrate G., Krieg A., Faustin B., Loeffler M., Godzik A., Krajewski S., Reed J. C. ( 2008). ChlaDub1 of Chlamydia trachomatis suppresses NF-κB activation and inhibits IκBα ubiquitination and degradation. Cell Microbiol 10:1879–1892 [View Article][PubMed]
    [Google Scholar]
  18. Marks D. J., Rahman F. Z., Sewell G. W., Segal A. W. ( 2010). Crohn’s disease: an immune deficiency state. Clin Rev Allergy Immunol 38:20–31 [View Article][PubMed]
    [Google Scholar]
  19. Patrick S. ( 2002). Bacteroides. Molecular Medical Microbiology1921–1948 Sussman M. London: Academic Press; [View Article]
    [Google Scholar]
  20. Patrick S., Duerden B. I. ( 2006). Gram-negative non-spore forming obligate anaerobes. Principles and Practice of Clinical Bacteriology, 2nd edn.541–556 Gillespie S. H., Hawkey P. London: Wiley; [View Article]
    [Google Scholar]
  21. Patrick S., McKenna J. P., O’Hagan S., Dermott E. ( 1996). A comparison of the haemagglutinating and enzymic activities of Bacteroides fragilis whole cells and outer membrane vesicles. Microb Pathog 20:191–202 [View Article][PubMed]
    [Google Scholar]
  22. Patrick S., Houston S., Thacker Z., Blakely G. W. ( 2009). Mutational analysis of genes implicated in LPS and capsular polysaccharide biosynthesis in the opportunistic pathogen Bacteroides fragilis. Microbiology 155:1039–1049 [View Article][PubMed]
    [Google Scholar]
  23. Patrick S., Blakely G. W., Houston S., Moore J., Abratt V. R., Bertalan M., Cerdeño-Tárraga A. M., Quail M. A., Corton N. et al. & other authors ( 2010). Twenty-eight divergent polysaccharide loci specifying within- and amongst-strain capsule diversity in three strains of Bacteroides fragilis. Microbiology 156:3255–3269 [View Article][PubMed]
    [Google Scholar]
  24. Pearce M. J., Mintseris J., Ferreyra J., Gygi S. P., Darwin K. H. ( 2008). Ubiquitin-like protein involved in the proteasome pathway of Mycobacterium tuberculosis. Science 322:1104–1107 [View Article][PubMed]
    [Google Scholar]
  25. Perrin A. J., Jiang X., Birmingham C. L., So N. S., Brumell J. H. ( 2004). Recognition of bacteria in the cytosol of Mammalian cells by the ubiquitin system. Curr Biol 14:806–811 [View Article][PubMed]
    [Google Scholar]
  26. Rodríguez J. E., Schisler J. C., Patterson C., Willis M. S. ( 2009). Seek and destroy: the ubiquitin–proteasome system in cardiac disease. Curr Hypertens Rep 11:396–405 [View Article][PubMed]
    [Google Scholar]
  27. Rytkönen A., Poh J., Garmendia J., Boyle C., Thompson A., Liu M., Freemont P., Hinton J. C., Holden D. W. ( 2007). SseL, a Salmonella deubiquitinase required for macrophage killing and virulence. Proc Natl Acad Sci U S A 104:3502–3507 [View Article][PubMed]
    [Google Scholar]
  28. Schwartz A. L., Ciechanover A. ( 2009). Targeting proteins for destruction by the ubiquitin system: implications for human pathobiology. Annu Rev Pharmacol Toxicol 49:73–96 [View Article][PubMed]
    [Google Scholar]
  29. Shaw M. H., Reimer T., Kim Y.-G., Nuñez G. ( 2008). NOD-like receptors (NLRs): bona fide intracellular microbial sensors. Curr Opin Immunol 20:377–382 [View Article][PubMed]
    [Google Scholar]
  30. Swidsinski A., Weber J., Loening-Baucke V., Hale L. P., Lochs H. ( 2005). Spatial organization and composition of the mucosal flora in patients with inflammatory bowel disease. J Clin Microbiol 43:3380–3389 [View Article][PubMed]
    [Google Scholar]
  31. Tasaki T., Mulder L. C., Iwamatsu A., Lee M. J., Davydov I. V., Varshavsky A., Muesing M., Kwon Y. T. ( 2005). A family of mammalian E3 ubiquitin ligases that contain the UBR box motif and recognize N-degrons. Mol Cell Biol 25:7120–7136 [View Article][PubMed]
    [Google Scholar]
  32. Van Tassell R. L., Wilkins T. D. ( 1978). Isolation of auxotrophs of Bacteroides fragilis. Can J Microbiol 24:1619–1621 [View Article][PubMed]
    [Google Scholar]
  33. Vereecke L., Beyaert R., van Loo G. ( 2009). The ubiquitin-editing enzyme A20 (TNFAIP3) is a central regulator of immunopathology. Trends Immunol 30:383–391 [View Article][PubMed]
    [Google Scholar]
  34. Xavier R. J., Podolsky D. K. ( 2007). Unravelling the pathogenesis of inflammatory bowel disease. Nature 448:427–434 [View Article][PubMed]
    [Google Scholar]
  35. Zhang Y., Higashide W. M., McCormick B. A., Chen J., Zhou D. ( 2006). The inflammation-associated Salmonella SopA is a HECT-like E3 ubiquitin ligase. Mol Microbiol 62:786–793 [View Article][PubMed]
    [Google Scholar]
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