Project Details
Projekt
Unraveling the arsenal and mechanisms that Bacteroidetes use for kin competition
Applicant
Athanasios Typas, Ph.D.
Subject Area
Metabolism, Biochemistry and Genetics of Microorganisms
Term
since 2025
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 564429022
We have traditionally studied microbial physiology and functions in reductionist ways –growing microbes in isolation under well-controlled conditions. It is thus not surprising that functions relevant for interactions with other microbes, predators (e.g. phages) or hosts have remained understudied, despite their relevance in nature and the strong selection pressure to evolve (to bypass defense mechanisms). It is tempting to speculate that such “interaction-related” functions constitute a significant part of the remaining “unknowns” in microbial genomes. For the human gut microbiota these functions are of particular interest, as microbes form complex stable communities in a dynamic environment, where they interact with the host and other community members, and fend off incoming microbes from food. From work mostly on model enterobacteria, it has become evident that phylogenetically similar species and strains of the same species strongly compete with each other for the same niche, and use different ways to eliminate each other. In preliminary work using a strain collection of one of the most abundant and prevalent bacterial species in the human gut, Phocaeicola vulgatus, and a quantitative high-throughput interaction assay, we demonstrate that intraspecies interactions are common, new toxins can be predicted by clustering inhibition patterns, and their biosynthetic genomic loci can be identified using arrayed mutant libraries. In this grant, we aim to investigate the mechanisms behind the biosynthesis, maturation, export, immunity and mode-of-action of a new toxin (bacteriocin) of P. vulgatus we discovered, using a combination of molecular and biochemical approaches. We also want to expand our discovery pipeline for identification of diffusible toxins by increasing the size of our strain collections and expanding to other abundant and prevalent Bacteroides (B. uniformis), and by utilizing our established ability to construct and deconvolute genome-wide mutant libraries in the Bacteroidota phylum. Thereby we envision to provide a paradigm that can be applied to other gut microbes, and contribute to dissecting interactions that shape the human gut microbiome, and are integral for its stability, individuality and colonization resistance. In addition to illuminating a diverse class of elusive gene functions in the human gut microbiome, we will also provide tools for future strategies that aim at precise microbiome modulation. This project will benefit tremendously by technologies and approaches developed, and concepts emerging in this SPP for similar questions pertaining to interactions of other non-model gut microbes.
DFG Programme
Priority Programmes
Co-Investigator
Dr. Carlos Voogdt
