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

• Published in: Nature communications Vol. 15; no. 1; pp. 2041 - 11
• Main Authors: Strausz, Satu, Abner, Erik, Blacker, Grace, Galloway, Sarah, Hansen, Paige, Feng, Qingying, Lee, Brandon T., Jones, Samuel E., Haapaniemi, Hele, Raak, Sten, Nahass, George Ronald, Sanders, Erin, Soodla, Pilleriin, Võsa, Urmo, Esko, Tõnu, Sinnott-Armstrong, Nasa, Weissman, Irving L., Daly, Mark, Aivelo, Tuomas, Tal, Michal Caspi, Ollila, Hanna M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 19.03.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 45/43; 631/208; 631/250; Animals; Bacteria; Borrelia; Borrelia burgdorferi; Borrelia burgdorferi - genetics; Epidemiology; Humanities and Social Sciences; Humans; Infections; Ixodes - microbiology; Lyme disease; Lyme Disease - microbiology; Mice; multidisciplinary; Parasitic diseases; Proteins; Science; Science (multidisciplinary); Secretions; Secretoglobins; Susceptibility; Tick-borne diseases; Vector-borne diseases
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-45983-9

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. The genetic basis of susceptibility to Lyme disease is largely unknown. Here, the authors discover a risk locus in the gene encoding the protein Secretoglobin family 1D member 2, which is expressed in skin and affects infection by the bacteria that causes Lyme disease in vitro and in vivo.