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Dryad

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

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Jul 04, 2024 version files 3.48 KB
Jul 26, 2024 version files 3.88 KB

Abstract

The microbiome holds great promise as a source of novel therapeutic targets for many diseases. Mining for causative microorganisms that impact processes underlying disease states should utilize Koch’s postulates. Here we show a functional screen for the bacterial microbiota of intestinal immunoglobulin A (IgA)-deficient mice; we identified a novel Gram-negative bacterium, proposed to be named as Tomasiella immunophila that induces and degrades IgA in mouse intestine. T. immunophila is auxotrophic for the bacterial cell wall amino sugar N-acetylmuramic acid (MurNAc). T. immunophila secretes IgA-degrading enzymes into outer membrane vesicles that preferentially degrade rodent antibodies with kappa but not lambda light chains. We propose this study uncovers a new paradigm for the role of symbionts in immunodeficiency that can ultimately be applied to human disease.