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

© 2024. The Author(s)..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:15

Enthalten in:

Nature communications - 15(2024), 1 vom: 19. März, Seite 2041

Sprache:

Englisch

Beteiligte Personen:

Strausz, Satu [VerfasserIn]
Abner, Erik [VerfasserIn]
Blacker, Grace [VerfasserIn]
Galloway, Sarah [VerfasserIn]
Hansen, Paige [VerfasserIn]
Feng, Qingying [VerfasserIn]
Lee, Brandon T [VerfasserIn]
Jones, Samuel E [VerfasserIn]
Haapaniemi, Hele [VerfasserIn]
Raak, Sten [VerfasserIn]
Nahass, George Ronald [VerfasserIn]
Sanders, Erin [VerfasserIn]
FinnGen [VerfasserIn]
Estonian Genome Centre [VerfasserIn]
Estonian Biobank Research Team [VerfasserIn]
Soodla, Pilleriin [VerfasserIn]
Võsa, Urmo [VerfasserIn]
Esko, Tõnu [VerfasserIn]
Sinnott-Armstrong, Nasa [VerfasserIn]
Weissman, Irving L [VerfasserIn]
Daly, Mark [VerfasserIn]
Aivelo, Tuomas [VerfasserIn]
Tal, Michal Caspi [VerfasserIn]
Ollila, Hanna M [VerfasserIn]

Links:

Volltext

Themen:

Journal Article
SCGB1D2 protein, human
Secretoglobins

Anmerkungen:

Date Completed 21.03.2024

Date Revised 23.03.2024

published: Electronic

Citation Status MEDLINE

doi:

10.1038/s41467-024-45983-9

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM369933451