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

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; FinnGen; Estonian Genome Centre; Estonian Biobank Research Team; Pilleriin Soodla; Urmo Võsa; Tõnu Esko; Nasa Sinnott-Armstrong; Irving L Weissman; Mark Daly; Tuomas Aivelo; Michal Caspi Tal; Hanna M Ollila

doi:10.1038/s41467-024-45983-9

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

Nat Commun. 2024 Mar 19;15(1):2041. doi: 10.1038/s41467-024-45983-9.

Authors

Satu Strausz^{1

2

3

4}, Erik Abner^#⁵, Grace Blacker^#⁶, Sarah Galloway^#⁶, Paige Hansen^#^{6

7}, Qingying Feng⁷, Brandon T Lee^{6

7}, Samuel E Jones¹, Hele Haapaniemi¹, Sten Raak⁵, George Ronald Nahass^{6

7

8}, Erin Sanders^{6

7}; FinnGen; Estonian Genome Centre; Estonian Biobank Research Team; Pilleriin Soodla⁹, Urmo Võsa⁵, Tõnu Esko⁵, Nasa Sinnott-Armstrong^{1

2

10}, Irving L Weissman⁶, Mark Daly¹, Tuomas Aivelo¹¹, Michal Caspi Tal^{12

13}, Hanna M Ollila^{14

15

16

17}

Affiliations

¹ Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.
² Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
³ Department of Oral and Maxillofacial Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
⁴ Department of Plastic Surgery, Cleft Palate and Craniofacial Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
⁵ Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
⁶ Institute for Stem Cell Biology & Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.
⁷ Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁸ Richard and Loan Hill Department of Biomedical Engineering, University of Illinois at Chicago, Chicago, IL, USA.
⁹ Department of Infectious Diseases, Internal Medicine Clinic, Tartu University Hospital, Tartu, Estonia.
¹⁰ Herbold Computational Biology Program, Fred Hutchinson Cancer Center, Seattle, WA, USA.
¹¹ Organismal and Evolutionary Biology Research Program, University of Helsinki, Helsinki, Finland.
¹² Institute for Stem Cell Biology & Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA. [email protected].
¹³ Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. [email protected].
¹⁴ Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland. [email protected].
¹⁵ Broad Institute of MIT and Harvard, Cambridge, Massachusetts, MA, USA. [email protected].
¹⁶ Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA. [email protected].
¹⁷ Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. [email protected].

^# Contributed equally.

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.

MeSH terms

Animals
Borrelia burgdorferi* / genetics
Humans
Ixodes* / microbiology
Lyme Disease* / microbiology
Mice
Secretoglobins*

Substances

SCGB1D2 protein, human
Secretoglobins

Grants and funding

#340538/Academy of Finland (Suomen Akatemia)