Bacteroides fragilis is a Gram negative strictly anaerobic, opportunistic bacterial pathogen found in the microbiota of the human GI tract. We have discovered a gene (ubb) encoding a protein designated BfUbb, with 63% identity to human ubiquitin (Hubb). Ubiquitin is a highly conserved protein which until this discovery, has been found only in eukaryotes. Ubiquitin tagging of proteins governs nearly every eukaryotic cell function and is also involved in development and function of the immune system. To date, B. fragilis is unique in being the only bacterium to encode an identified ubiquitin homologue. We have recently shown that BfUbb and Hubb are predicted to be structurally highly similar and may have cross reactive and unique epitopes, and that BfUbb can generate an IgG response in humans, with patients referred for autoimmune disease testing more likely to have high levels of IgG reactive with BfUbb than healthy volunteers. This suggests a potential relationship of Bfubb with human disease.
The aims of this study are:
(i) map the cross reactive epitopes of Bfubb and Hubb
(ii) identify the unique epitopes of Bfubb
(iii) determine the functional activity of Bfubb by (i) investigating antimicrobial activity, and (ii) by using an in vitro model approach to determine how Bfubb moves across the gut barrier, its impact on various cell lines, and if and how antibodies to Bfubb and Hubb influence cellular activity.
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