Evidence map›Paper›PMID 39675703›Full record

ArticleThe Journal of biological chemistry2025

CspZ variant-specific interaction with factor H incorporates a metal site to support Lyme borreliae complement evasion.

Kalvis Brangulis, Valerie Sürth, Ashley L Marcinkiewicz, Inara Akopjana, Andris Kazaks, Janis Bogans, Alisa Huber, Yi-Pin Lin, Peter Kraiczy

Abstract read
In one paragraph

Article in The Journal of biological chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Borrelia surface proteins: new horizons in Lyme disease diagnosis.Applied microbiology and biotechnology · 2025
    Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Kalvis BrangulisLatvian Biomedical Research and Study Centre, Riga, Latvia; Department of Human Physiology and Biochemistry, Riga Stradins University, Riga, Latvia. Electronic address: kalvis@biomed.lu.lv.
Valerie SürthGoethe University Frankfurt, University Hospital of Frankfurt, Institute of Medical Microbiology and Infection Control, Frankfurt, Germany.
Ashley L MarcinkiewiczDivision of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany, New York, USA; Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts, USA.
Inara AkopjanaLatvian Biomedical Research and Study Centre, Riga, Latvia.
Andris KazaksLatvian Biomedical Research and Study Centre, Riga, Latvia.
Janis BogansLatvian Biomedical Research and Study Centre, Riga, Latvia.
Alisa HuberGoethe University Frankfurt, University Hospital of Frankfurt, Institute of Medical Microbiology and Infection Control, Frankfurt, Germany.
Yi-Pin LinDivision of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany, New York, USA; Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts, USA; Department of Biomedical Sciences, SUNY Albany, Albany, New York, USA. Electronic address: Yi-Pin.Lin@tufts.edu.
Peter KraiczyGoethe University Frankfurt, University Hospital of Frankfurt, Institute of Medical Microbiology and Infection Control, Frankfurt, Germany. Electronic address: Kraiczy@em.uni-frankfurt.de.

Funding

Immunomodulatory mechanisms of wild bird reservoir hosts that facilitate persistence of Lyme disease bacteriaR01AI181746 · NIAID · TUFTS UNIVERSITY BOSTON · PI Yi-Pin Lin · 2024 to 2026
$2.5M
Identification of the mechanism of protection against a B. burgdorferi protein CspZ for the prevention of Lyme diseaseR21AI144891 · NIAID · WADSWORTH CENTER · PI BOTTAZZI, MARIA ELENA, LIN, YI-PIN · 2020 to 2021
$441k
NIAID NIH HHS R01 AI181746NIAID NIH HHS R21 AI144891
6 · The paper itself

Abstract

Polymorphic microbial immune evasion proteins dictate the pathogen species- or strain-specific virulence. Metals can impact how microbial proteins confer host-pathogen interactions, but whether this activity can be allelically variable is unclear. Here, we investigate the polymorphic CspZ protein of Lyme disease spirochete bacteria to assess the role of metals in protein-protein interaction. CspZ facilitates evasion of the complement system, the first line of immune defense through binding to the complement regulator factor H (FH). By obtaining a high-resolution cocrystal CspZ-FH structure, we identified a zinc coordinating the binding of FH SCR6-7 domains to a Glu65 on a loop from CspZ of Borrelia burgdorferi B31. However, zinc is dispensable for human FH binding for CspZ orthologs with a different loop orientation and/or lacking this glutamate. Phylogenetic analysis of all known human FH-binding CspZ variants further grouped the proteins into three unique lineages correlating with loop sequences. This suggests multiple FH-binding mechanisms evolved through Lyme disease spirochete-host interactions. Overall, this multidisciplinary work elucidates how the allelically specific immune evasion role of metals is impacted by microbial protein polymorphisms.

Indexed as

Bacterial ProteinsBorrelia burgdorferiComplement Factor HImmune EvasionLyme DiseaseZincBinding SitesCrystallography, X-RayHumansPhylogenyProtein BindingBacterial ProteinsComplement Factor HZincbacterial pathogenesisBorreliacomplementfactor HLyme diseasespirochetezinc

Identifiers

PMID39675703
PMCPMC11773018

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.