Targeted Design and Manipulation of Minimal Bacterial Consortia for Strain Replacement within Microbiomes
As part of CRC1371 Microbiome Signatures , project P14 focuses on the targeted modulation of synthetic microbial communities (SYNs) through personalized strategies for strain-level replacement in complex mouse and human microbiomes. Our approach combines bacteriophage therapy with the introduction of niche-competitive bacterial strains to selectively replace target taxa. The primary focus will be on clinically relevant groups such as Enterobacteriaceae and enterococci, due to their roles in infections, antimicrobial resistance, and chronic inflammation. In addition, we will expand this strategy to the commensal species Phocaeicola vulgatus (formerly Bacteroides vulgatus), a genetically tractable and prevalent member of the core gut microbiota in mice and humans. This will allow us to study bacterial traits that influence strain engraftment and to manipulate specific ecosystem functions, such as complex carbohydrate metabolism and proinflammatory activity.
Principal Investigators: Thomas Clavel (RWTH), Prof. Bärbel Stecher
An increasing number of human diseases is associated with an altered intestinal microbiota. The microbiota consists of trillions of microbes including viruses amongst which bacteriophages (phages) that predate on bacteria are the most abundant. Phages are important effectors and indicators of human health and disease by managing specific bacterial population structures and by interacting with the mucosal immune system. Although metagenome-based studies have addressed their abundance, diversity and stability over time in the gut, little is known on the role of phages in microbiome homeostasis and their impact on global microbiome functions. To overcome this limitation, we employ the OMM model and strain-specific phages in stably colonized gnotobiotic mice. We will conduct an in-depth characterization of phage ecology and study their influence on the microbiome and related functions in the gut. In addition, we study the mechanisms underlying stable coexistence of phages and their host bacteria in the gut. The final goal is to refine strategies for phage-based microbiome engineering. In PhaStGut, a DFG-ANR funded project, we collaborate in an interdisciplinary team of four partners combining meta-transcriptomics, meta-metabolomics and 3D DNA capture in gnotobiotic mice. Thereby, we will uncover mechanisms governing the dynamic interplay between phages and their host bacteria that shape the mammalian microbiota.
Principal Investigators: Laurent Débarbieux, Institut Pasteur, France (Coordinator), Martial Marbouty, Institut Pasteur, France, Alesia Walker, Helmholtz Institute, Germany