A benign resident or the enemy within: the Bacteroides fragilis homologue of eukaryotic ubiquitin

The unexpected discovery of a bacterial version of eukaryotic ubiquitin in the human gastrointestinal (GI) tract resident, Bacteroides fragilis , raises the intriguing possibility of a novel trigger of human disease of unknown cause. In eukaryotes, ubiquitin is essential for normal intracellular function. In addition, extracellular ubiquitin is necessary for fertility, and there is growing evidence for its role as an immunomodulator. The B. fragilis version of ubiquitin (BfUbb) is exported from the bacterial cell and, within the GI tract, is involved in interspecies competition. This perspective addresses the potential impact of BfUbb on human health. The amino acid sequence of BfUbb is 84% similar to human ubiquitin and crystallography reveals a ubiquitin-like structure. This structural mimicry is reflected in immunological cross-reactivity with mammalian ubiquitin. Antibodies that bind to BfUbb can be detected in human serum, for example, in individuals diagnosed with immune-mediated inflammatory disease. Given the essential role of ubiquitin in human life, health and well-being, this perspective will highlight where the study of BfUbb could reveal key insights into human diseases which currently lack a full understanding and address potential challenges. A better understanding of BfUbb interactions in relation to the immune system interactions could prove to be wide-reaching in relation to disease prevention, detection and treatment.