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SCGB1D2 inhibits growth of Borrelia burgdorferi and affects susceptibility to Lyme disease

Author

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  • Satu Strausz

    (Helsinki Institute of Life Science, University of Helsinki
    Stanford University School of Medicine
    Helsinki University Hospital and University of Helsinki
    Cleft Palate and Craniofacial Center, Helsinki University Hospital and University of Helsinki)

  • Erik Abner

    (Institute of Genomics, University of Tartu)

  • Grace Blacker

    (Stanford University School of Medicine)

  • Sarah Galloway

    (Stanford University School of Medicine)

  • Paige Hansen

    (Stanford University School of Medicine
    Massachusetts Institute of Technology)

  • Qingying Feng

    (Massachusetts Institute of Technology)

  • Brandon T. Lee

    (Stanford University School of Medicine
    Massachusetts Institute of Technology)

  • Samuel E. Jones

    (Helsinki Institute of Life Science, University of Helsinki)

  • Hele Haapaniemi

    (Helsinki Institute of Life Science, University of Helsinki)

  • Sten Raak

    (Institute of Genomics, University of Tartu)

  • George Ronald Nahass

    (Stanford University School of Medicine
    Massachusetts Institute of Technology
    University of Illinois at Chicago)

  • Erin Sanders

    (Stanford University School of Medicine
    Massachusetts Institute of Technology)

  • Pilleriin Soodla

    (Internal Medicine Clinic, Tartu University Hospital)

  • Urmo Võsa

    (Institute of Genomics, University of Tartu)

  • Tõnu Esko

    (Institute of Genomics, University of Tartu)

  • Nasa Sinnott-Armstrong

    (Helsinki Institute of Life Science, University of Helsinki
    Stanford University School of Medicine
    Fred Hutchinson Cancer Center)

  • Irving L. Weissman

    (Stanford University School of Medicine)

  • Mark Daly

    (Helsinki Institute of Life Science, University of Helsinki)

  • Tuomas Aivelo

    (University of Helsinki)

  • Michal Caspi Tal

    (Stanford University School of Medicine
    Massachusetts Institute of Technology)

  • Hanna M. Ollila

    (Helsinki Institute of Life Science, University of Helsinki
    Broad Institute of MIT and Harvard, Cambridge
    Massachusetts General Hospital
    Massachusetts General Hospital and Harvard Medical School)

Abstract

Lyme disease is a tick-borne disease caused by bacteria of the genus Borrelia. The host factors that modulate susceptibility for Lyme disease have remained mostly unknown. Using epidemiological and genetic data from FinnGen and Estonian Biobank, we identify two previously known variants and an unknown common missense variant at the gene encoding for Secretoglobin family 1D member 2 (SCGB1D2) protein that increases the susceptibility for Lyme disease. Using live Borrelia burgdorferi (Bb) we find that recombinant reference SCGB1D2 protein inhibits the growth of Bb in vitro more efficiently than the recombinant protein with SCGB1D2 P53L deleterious missense variant. Finally, using an in vivo murine infection model we show that recombinant SCGB1D2 prevents infection by Borrelia in vivo. Together, these data suggest that SCGB1D2 is a host defense factor present in the skin, sweat, and other secretions which protects against Bb infection and opens an exciting therapeutic avenue for Lyme disease.

Suggested Citation

  • Satu Strausz & Erik Abner & Grace Blacker & Sarah Galloway & Paige Hansen & Qingying Feng & Brandon T. Lee & Samuel E. Jones & Hele Haapaniemi & Sten Raak & George Ronald Nahass & Erin Sanders & Pille, 2024. "SCGB1D2 inhibits growth of Borrelia burgdorferi and affects susceptibility to Lyme disease," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45983-9
    DOI: 10.1038/s41467-024-45983-9
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    References listed on IDEAS

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    1. Chao Tian & Bethann S. Hromatka & Amy K. Kiefer & Nicholas Eriksson & Suzanne M. Noble & Joyce Y. Tung & David A. Hinds, 2017. "Genome-wide association and HLA region fine-mapping studies identify susceptibility loci for multiple common infections," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    2. Gao Wang & Abhishek Sarkar & Peter Carbonetto & Matthew Stephens, 2020. "A simple new approach to variable selection in regression, with application to genetic fine mapping," Journal of the Royal Statistical Society Series B, Royal Statistical Society, vol. 82(5), pages 1273-1300, December.
    3. Mitja I. Kurki & Juha Karjalainen & Priit Palta & Timo P. Sipilä & Kati Kristiansson & Kati M. Donner & Mary P. Reeve & Hannele Laivuori & Mervi Aavikko & Mari A. Kaunisto & Anu Loukola & Elisa Lahtel, 2023. "FinnGen provides genetic insights from a well-phenotyped isolated population," Nature, Nature, vol. 613(7944), pages 508-518, January.
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