IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-45983-9.html
   My bibliography  Save this article

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

Author

Listed:
  • 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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-45983-9
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-45983-9?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Linda Ottensmann & Rubina Tabassum & Sanni E. Ruotsalainen & Mathias J. Gerl & Christian Klose & Elisabeth Widén & Kai Simons & Samuli Ripatti & Matti Pirinen, 2023. "Genome-wide association analysis of plasma lipidome identifies 495 genetic associations," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Javier Botey-Bataller & Hedwig D. Vrijmoeth & Jeanine Ursinus & Bart-Jan Kullberg & Cees C. Wijngaard & Hadewych Hofstede & Ahmed Alaswad & Manoj K. Gupta & Lennart M. Roesner & Jochen Huehn & Thomas , 2024. "A comprehensive genetic map of cytokine responses in Lyme borreliosis," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    3. Chirag Krishna & Joshua Chiou & Saori Sakaue & Joyce B. Kang & Stephen M. Christensen & Isac Lee & Melis Atalar Aksit & Hye In Kim & David Schack & Soumya Raychaudhuri & Daniel Ziemek & Xinli Hu, 2024. "The influence of HLA genetic variation on plasma protein expression," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    4. Natalie DeForest & Yuqi Wang & Zhiyi Zhu & Jacqueline S. Dron & Ryan Koesterer & Pradeep Natarajan & Jason Flannick & Tiffany Amariuta & Gina M. Peloso & Amit R. Majithia, 2024. "Genome-wide discovery and integrative genomic characterization of insulin resistance loci using serum triglycerides to HDL-cholesterol ratio as a proxy," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    5. Sylvia Hartmann & Summaira Yasmeen & Benjamin M. Jacobs & Spiros Denaxas & Munir Pirmohamed & Eric R. Gamazon & Mark J. Caulfield & Harry Hemingway & Maik Pietzner & Claudia Langenberg, 2023. "ADRA2A and IRX1 are putative risk genes for Raynaud’s phenomenon," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    6. Xingjie Hao & Zhonghe Shao & Ning Zhang & Minghui Jiang & Xi Cao & Si Li & Yunlong Guan & Chaolong Wang, 2023. "Integrative genome-wide analyses identify novel loci associated with kidney stones and provide insights into its genetic architecture," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    7. Ruoyu Tian & Tian Ge & Hyeokmoon Kweon & Daniel B. Rocha & Max Lam & Jimmy Z. Liu & Kritika Singh & Daniel F. Levey & Joel Gelernter & Murray B. Stein & Ellen A. Tsai & Hailiang Huang & Christopher F., 2024. "Whole-exome sequencing in UK Biobank reveals rare genetic architecture for depression," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    8. Tuomo Hartonen & Bradley Jermy & Hanna Sõnajalg & Pekka Vartiainen & Kristi Krebs & Andrius Vabalas & Tuija Leino & Hanna Nohynek & Jonas Sivelä & Reedik Mägi & Mark Daly & Hanna M. Ollila & Lili Mila, 2023. "Nationwide health, socio-economic and genetic predictors of COVID-19 vaccination status in Finland," Nature Human Behaviour, Nature, vol. 7(7), pages 1069-1083, July.
    9. Shiyu Zhang & Zheng Wang & Yijing Wang & Yixiao Zhu & Qiao Zhou & Xingxing Jian & Guihu Zhao & Jian Qiu & Kun Xia & Beisha Tang & Julian Mutz & Jinchen Li & Bin Li, 2024. "A metabolomic profile of biological aging in 250,341 individuals from the UK Biobank," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    10. Bingxin Zhao & Yujue Li & Zirui Fan & Zhenyi Wu & Juan Shu & Xiaochen Yang & Yilin Yang & Xifeng Wang & Bingxuan Li & Xiyao Wang & Carlos Copana & Yue Yang & Jinjie Lin & Yun Li & Jason L. Stein & Joa, 2024. "Eye-brain connections revealed by multimodal retinal and brain imaging genetics," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    11. Isabelle Austin-Zimmerman & Daniel F. Levey & Olga Giannakopoulou & Joseph D. Deak & Marco Galimberti & Keyrun Adhikari & Hang Zhou & Spiros Denaxas & Haritz Irizar & Karoline Kuchenbaecker & Andrew M, 2023. "Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    12. Dmitrii Usoltsev & Nikita Kolosov & Oxana Rotar & Alexander Loboda & Maria Boyarinova & Ekaterina Moguchaya & Ekaterina Kolesova & Anastasia Erina & Kristina Tolkunova & Valeriia Rezapova & Ivan Molot, 2024. "Complex trait susceptibilities and population diversity in a sample of 4,145 Russians," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    13. Wenhan Chen & Yang Wu & Zhili Zheng & Ting Qi & Peter M. Visscher & Zhihong Zhu & Jian Yang, 2021. "Improved analyses of GWAS summary statistics by reducing data heterogeneity and errors," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    14. Nathan LaPierre & Kodi Taraszka & Helen Huang & Rosemary He & Farhad Hormozdiari & Eleazar Eskin, 2021. "Identifying causal variants by fine mapping across multiple studies," PLOS Genetics, Public Library of Science, vol. 17(9), pages 1-19, September.
    15. Mary P. LaPierre & Katherine Lawler & Svenja Godbersen & I. Sadaf Farooqi & Markus Stoffel, 2022. "MicroRNA-7 regulates melanocortin circuits involved in mammalian energy homeostasis," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    16. Yunfeng Huang & Dora Bodnar & Chia-Yen Chen & Gabriela Sanchez-Andrade & Mark Sanderson & Jun Shi & Katherine G. Meilleur & Matthew E. Hurles & Sebastian S. Gerety & Ellen A. Tsai & Heiko Runz, 2023. "Rare genetic variants impact muscle strength," Nature Communications, Nature, vol. 14(1), pages 1-8, December.
    17. Huiying He & Yue Leng & Xinglan Cao & Yiwang Zhu & Xiaoxia Li & Qiaoling Yuan & Bin Zhang & Wenchuang He & Hua Wei & Xiangpei Liu & Qiang Xu & Mingliang Guo & Hong Zhang & Longbo Yang & Yang Lv & Xian, 2024. "The pan-tandem repeat map highlights multiallelic variants underlying gene expression and agronomic traits in rice," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    18. Joel T. Rämö & Tuomo Kiiskinen & Richard Seist & Kristi Krebs & Masahiro Kanai & Juha Karjalainen & Mitja Kurki & Eija Hämäläinen & Paavo Häppölä & Aki S. Havulinna & Heidi Hautakangas & Reedik Mägi &, 2023. "Genome-wide screen of otosclerosis in population biobanks: 27 loci and shared associations with skeletal structure," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    19. William R. Reay & Dylan J. Kiltschewskij & Maria A. Biase & Zachary F. Gerring & Kousik Kundu & Praveen Surendran & Laura A. Greco & Erin D. Clarke & Clare E. Collins & Alison M. Mondul & Demetrius Al, 2024. "Genetic influences on circulating retinol and its relationship to human health," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    20. Abolfazl Doostparast Torshizi & Dongnhu T. Truong & Liping Hou & Bart Smets & Christopher D. Whelan & Shuwei Li, 2024. "Proteogenomic network analysis reveals dysregulated mechanisms and potential mediators in Parkinson’s disease," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45983-9. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.