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Young, V. ; Dohai, B.S.M. ; Halder, H. ; Fernandez-Macgregor, J.* ; van Heusden, N.S.* ; Hitch, T.C.A.* ; Weller, B. ; Hyden, P.* ; Saha, D.* ; Pieren, D.K.J.* ; Rittchen, S.* ; Lambourne, L.* ; Maseko, S.B.* ; Lin, C.-W. ; Tun, Y.M. ; Bibus, J.* ; Pletschacher, L. ; Boujeant, M.* ; Choteau, S.A.* ; Bergogne, L.* ; Perrin, J.* ; Ober, F. ; Schwehn, P. ; Rothballer, S.T. ; Altmann, M. ; Altmann, S. ; Strobel, A. ; Rothballer, M. ; Tofaute, M.J. ; Kotlarz, D.M. ; Heinig, M. ; Clavel, T.* ; Calderwood, M.A.* ; Vidal, M.* ; Twizere, J.C.* ; Vincentelli, R.* ; Krappmann, D. ; Boes, M.* ; Falter, C. ; Rattei, T.* ; Brun, C.* ; Zanzoni, A.* ; Falter-Braun, P.

Effector-host interactome map links type III secretion systems in healthy gut microbiomes to immune modulation.

Nat. Microbiol. 11, 442-460 (2026)
Verlagsversion Forschungsdaten DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
Pseudomonadota (formerly Proteobacteria) are prevalent in the commensal human gut microbiota, but also include many pathogens that rely on secretion systems to support pathogenicity by injecting proteins into host cells. Here we show that 80% of Pseudomonadota from healthy gut microbiomes also have intact type III secretion systems (T3SS). Candidate effectors predicted by machine learning display sequence and structural features that are distinct from those of pathogen effectors. Towards a systems-level functional understanding, we experimentally constructed a protein-protein meta-interactome map between human proteins and commensal effectors. Network analyses uncovered that effector-targeted neighbourhoods are enriched for genetic variation linked to microbiome-associated conditions, including autoimmune and metabolic diseases. Metagenomic analysis revealed effector enrichment in Crohn's disease but depletion in ulcerative colitis. Functionally, commensal effectors can translocate into human cells and modulate NF-κB signalling and cytokine secretion in vitro. Our findings indicate that T3SS contribute to microorganism-host cohabitation and that effector-host protein interactions may represent an underappreciated route by which commensal gut microbiota influences health.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Protein; Database; Network; Genomes; Prediction; Evolution; Catalog; Domains
ISSN (print) / ISBN 2058-5276
e-ISSN 2058-5276
Zeitschrift Nature microbiology
Quellenangaben Band: 11, Heft: 2, Seiten: 442-460 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Network Biology (INET)
Research Unit Signaling and Translation (SAT)
Institute of Translational Genomics (ITG)
Institute of Computational Biology (ICB)
Förderungen EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)
Agence Nationale de la Recherche (French National Research Agency)
Deutsche Forschungsgemeinschaft (German Research Foundation)
sterreichische Forschungsfrderungsgesellschaft (Austrian Research Promotion Agency)
Bundesministerium fr Bildung und Forschung (Federal Ministry of Education and Research)