A host-adapted auxotrophic gut symbiont induces mucosal immunodeficiency (Part I)

Harnessing the microbiome to benefit human health requires an initial step in determining the identify and function of causative microorganisms that impact specific host physiologic functions. Here we show a functional screen of the bacterial microbiota from mice with low intestinal immunoglobulin A (IgA) levels; we identified a Gram-negative bacterium, proposed as Tomasiella immunophila that induces and degrades IgA in mouse intestine. Mice harboring T. immunophila are susceptible to infections and show poor mucosal repair. T. immunophila is auxotrophic for the bacterial cell wall amino sugar N-acetylmuramic acid (MurNAc). It delivers immunoglobulin-degrading proteases into outer membrane vesicles that preferentially degrade rodent antibodies with kappa but not lambda light chains. This work indicates a role for symbionts in immunodeficiency, which might be applicable to human disease. , To screen for IgA-degrading bacteria from SIgA-Low mice (15), fecal samples were cultured anaerobically and plated on blood agar. Pools of bacterial colonies were then incubated with mouse monoclonal IgA and subjected to SDS-PAGE and immunoblot analysis. Pooled bacterial colonies showing IgA-degrading activity were tested individually again for cleavage activity. 16S rRNA gene sequencing revealed an IgA-degrading bacterium as a previously unknown species. Using the Genome Taxonomy Database Toolkit (GTDB-Tk), this bacterium was classified as the initial isolated representative of a previously undescribed genus within the Muribaculaceae family. Protologger (v1.3) was used to describe this novel taxon (51), which was proposed to be named Tomasiella immunophila. The bacterium and its outer membrane vesicles (OMVs) were visualized using transmission and scanning electron microscopy. Wild-type B6 mice were orally administered IgA-High fecal slurry with or without T. immunophila to test its in..., , # A host-adapted auxotrophic gut symbiont induces mucosal immunodeficiency

**[Access of dataset on Dryad:](https://doi.org/10.5061/dryad.j0zpc86p8)**

**[https://doi.org/10.5061/dryad.j0zpc86p8](https://doi.org/10.5061/dryad.j0zpc86p8),** raw data of main figure 2A,

**[https://doi.org/10.5061/dryad.bvq83bkj9](https://doi.org/10.5061/dryad.bvq83bkj9),** all additional raw experimental data are presented in the main and supplementary figures of the manuscript

**Summary of dataset contents:**

Two key datasets are included to provide all the data utilized in the manuscript supporting the conclusion that the bacterium *Tomasiella immunophila* is responsible for reduced levels of intestinal immunoglobulin A (IgA) in wild-type B6 mice and explores its biological impact on the host. The first dataset consists of the NEXUS file used to construct the phylogenetic tree (Fig. 2A). This tree is pivotal as it visually demonstrates the distinct separation of the novel genus, *Tomasiella*, from clo...