Interactions between intestinal commensal bacteria and different hosts: two sides of the same story

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Dokumentart: PhDThesis
Date: 2021-01-15
Language: English
Faculty: 7 Mathematisch-Naturwissenschaftliche Fakultät
Department: Biologie
Advisor: Frick, Julia-Stefanie (Prof. Dr.)
Day of Oral Examination: 2019-01-10
DDC Classifikation: 570 - Life sciences; biology
Keywords: Bakterien
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The gut microbiota crucially contributes to a variety of body functions: it supports nutrient digestion and influences the host immune system. It further impacts progression and/or the outcome of a variety of diseases. Inflammatory bowel diseases (IBD) are one of the most prominent microbiota-influenced diseases, which are accompanied by a compositional shift of the microbiota. A healthy human intestinal microbiota mostly consists of commensal bacteria with Firmicutes and Bacteroidetes making up the largest proportion. A balanced microbiota composition is important to maintain health benefits for the host. Commensals can be divided into symbionts and pathobionts. Symbionts are generally characterized by their beneficial immunomodulatory influence on the host, whereas pathobionts may negatively affect the host under certain circumstances therefore promoting intestinal inflammation. To characterize two model intestinal commensal bacterial species – symbiotic Bacteroides vulgatus mpk and pathobiotic Escherichia coli mpk – we sequenced the strains to analyze their respective genomes. The B. vulgatus mpk genome contains many different mobile genetic elements that have caused enormous genome diversification. Additionally we identified gene loci encoding for the formation of different outer membrane vesicles (OMVs) containing capsular polysaccharides that are produced under stress conditions to supporting bacterial survival. Further, we demonstrated that B. vulgatus mpk OMVs support immune priming of host cells therefore supporting intestinal immune homeostasis. Unlike B. vulgatus, E. coli strains are only poor gut colonizers during intestinal homeostasis but their accumulation is boosted during inflammation. We identified metabolic gene clusters in the E. coli mpk genome mediating bacterial survival during intestinal inflammation, most importantly the ethanolamine and 1,2-propanediol utilization clusters. Since vertebrates represent the most commonly used models to study microbe-host interactions we aimed to provide an alternative invertebrate host model, which is suitable to distinguish symbiotic from pathobiotic intestinal commensals. Therefore, we established an insect replacement model using the Galleria mellonella larva, which allows for the prediction of the immunogenic potential by commensal bacteria in mice.

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