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
2024-04-24
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