Project Details
Projekt
Functional adaptation of Phocaeicola vulgatus in response to metabolic injury and chronic inflammation
Subject Area
Metabolism, Biochemistry and Genetics of Microorganisms
Gastroenterology
Gastroenterology
Term
since 2025
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 564323824
Bacteroides and Phocaeicola species are prominent members of the human gut microbiota and have been implicated in health and diseases. In particular, Phocaeicola vulgatus has been highlighted as a pathobiont in inflammatory bowel diseases (IBD). However, genetic diversity, gene functions and mechanisms of host-microbe interaction are still largely missing for P. vulgatus. We hypothesize that the genomic plasticity and metabolic flexibility of P. vulgatus contribute to the functional adaptation of disease-relevant strains implicated in the initiation and progression of chronic inflammation. In this proposal, we aim to identify specific target genes of P. vulgatus required in the adaptation of these microbial-metabolic circuits. We will isolate human and mouse P. vulgatus strains and characterize their genomic, transcriptional and metabolic responses to milieu changes in the intestine during chronic inflammation in vitro and in vivo. Strains will be exposed in vitro to environmental stressors, such as oxidative and nitrosative stressors, first alone and then within minimal synthetic consortia. This will reveal adaptation mechanisms of P. vulgatus and how these are influenced by microbe-microbe interactions. To further explore the impact of P. vulgatus adaptation on host-microbial interactions, we will colonize germfree mouse models of metabolic injury (Hsp60Δ/ΔIEC) and chronic inflammation (Hsp60Δ/ΔIEC;Il10-/- mice) with selected P. vulgatus strains - alone or in combination with synthetic consortia. Finally, the most promising gene targets will be validated in vitro and in vivo using pooled transposon libraries and single mutants. Overall, this will allow us to identify adaptation mechanisms and functionally relevant gene targets of P. vulgatus in the context of changes in the gut environment during inflammation and their impact on initial and progressive IBD pathogenesis.
DFG Programme
Priority Programmes
