Abstract
Bacteroides fragilis is one of the most abundant Gram-negative bacteria in the human gut microbiota and has been associated with inflammatory bowel disease, colorectal cancer and various other diseases. Interestingly, the nontoxigenic counterpart of B. fragilis is increasingly suggested as a probiotic due to its beneficial interactions with the host. We hypothesized that this contradiction could be explained by the existence of diversifying subspecies or the exchange of mobile genetic elements encoding for pathogenic and virulence factors. In this master thesis research, we analysed the genomic diversity of B. fragilis aiming to comprehend the exceptional but varying properties of this species, which remain poorly understood. We first compiled all the available genomes from multiple geographic locations and sources into a large-scale dataset of over a thousand sequences. Phylogenetic and population structure analyses revealed numerous lineages, which were supported by pangenomic analyses, suggesting a common diversification of the core and accessory genomes, and reinforcing the concept of subspecies in B. fragilis. In total, we identified 18 distinct lineages, 15 of them were significantly associated with multidrug resistance encoding genes, and several others with distinct carbohydrate metabolism genes. Additionally, multiple mobile elements were detected containing virulence factors and stress resistance genes. In summary, our study confirms the widely underestimated genetic diversity of Bacteroides fragilis.
