Evidence map›Paper›PMID 40341334›Full record

ArticleNature microbiology2025

Typhoid toxin causes neuropathology by disrupting the blood-brain barrier.

Heng Zhao, Jonatas Catarino, Gabrielle Stack, Ashley Kristant Albizu, Maria Lara-Tejero, Tamas L Horvath, Jorge E Galán

Abstract read
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In one paragraph

Article in Nature microbiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

7 authors.

Heng ZhaoDepartment of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-7322-5513
Jonatas CatarinoDepartment of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-6542-7406
Gabrielle StackDepartment of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA.
Ashley Kristant AlbizuDepartment of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA.
Maria Lara-TejeroDepartment of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-1339-0859
Tamas L HorvathDepartment of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-7522-4602
Jorge E GalánDepartment of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA. jorge.galan@yale.edu.ORCID http://orcid.org/0000-0002-6531-0355

Funding

Typhoid Toxin and Salmonella Typhi pathogenesisR01AI114618 · NIAID · YALE UNIVERSITY · PI GALAN, JORGE E · 2014 to 2023
$5.4M
U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R01AI114618
6 · The paper itself

Abstract

Typhoid fever, primarily caused by Salmonella Typhi, can result in severe life-threatening complications such as encephalopathy. Here we elucidate the mechanisms by which typhoid toxin, a unique virulence factor of S. Typhi, mediates the neuropathology associated with typhoid fever. Utilizing mice engineered to have specific tissues protected from toxin action and an in vitro model of the blood-brain barrier (BBB), we demonstrate that, rather than direct action on neuronal or glial cells, typhoid toxin causes neuropathology by disrupting the BBB. Intravenous tracer studies confirmed significant BBB permeability changes following toxin exposure, an effect we found to be mediated by typhoid toxin's CdtB catalytic subunit. We demonstrate that corticosteroids are effective at mitigating BBB disruption in vivo, supporting their use for managing typhoid fever neurological complications. Our data reveal mechanistic insight into how typhoid toxin causes encephalopathy and suggest targeted therapeutic interventions to alleviate the severe neurological manifestations of typhoid fever.

Indexed as

Bacterial ToxinsBlood-Brain BarrierSalmonella typhiTyphoid FeverAnimalsDisease Models, AnimalHumansMiceNeuronsBacterial Toxins

Identifiers

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.