Evidence map›Paper›PMID 40155776›Full record

ArticleNature microbiology2025

ERK pathway reactivation prevents anthrax toxin lethality in mice.

Jie Liu, Zehua Zuo, Michael Ewing, Qing Cao, Liu Cao, Qi Li, Toren Finkel, Stephen H Leppla, Shihui Liu

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 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. Article
  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.

Jie LiuAging Institute of University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Zehua ZuoAging Institute of University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Michael EwingAging Institute of University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Qing CaoAging Institute of University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-6993-0789
Liu CaoHealth Sciences Institute, China Medical University, Shenyang, China.ORCID http://orcid.org/0000-0001-6471-1993
Qi LiAging Institute of University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Toren FinkelAging Institute of University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-0726-3546
Stephen H LepplaMicrobial Pathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Shihui LiuAging Institute of University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, PA, USA. SHL176@pitt.edu.ORCID http://orcid.org/0000-0003-3444-1069

Funding

Mechanisms of anthrax lethal toxin-induced mortality and the novel biological-based targeted therapiesR01AI170574 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Shihui Liu · 2023 to 2026
$2.4M
NIAID NIH HHS R01 AI170574U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R01AI170574
6 · The paper itself

Abstract

Lethal toxin (LT), the major virulence factor of Bacillus anthracis, proteolytically inactivates MEKs and disables downstream ERK, p38 and JNK pathway signalling leading to tissue damage and mortality. Therapies for LT-induced damage after host cell internalization of the toxin are lacking. Here we constructed MEK variants in which the LT proteolytic site was modified: MEK2(P10V/A11D), MEK3(I27D) and MEK6(I15D). These variants were resistant to proteolysis by LT. Expression in cells enabled sustained activation of ERK and p38 pathways and promoted cell survival upon LT treatment. Survival of LT- or B. anthracis-challenged MEK variant transgenic mice also increased compared with controls. We found that LT-mediated disruption of both ERK and p38 pathway is essential for anthrax pathogenesis. We show that engagement of upstream receptor tyrosine kinases reactivated the LT-disrupted ERK pathway, as did administering a cocktail of EGF, GM-CSF and FGF2 growth factors, which significantly increased survival of LT- or B. anthracis-challenged mice. These findings offer potential towards developing damage-limiting therapeutic strategies for anthrax.

Indexed as

AnthraxAntigens, BacterialBacillus anthracisBacterial ToxinsMAP Kinase Signaling SystemAnimalsDisease Models, AnimalHumansMiceMice, TransgenicSurvival Analysisanthrax toxinAntigens, BacterialBacterial Toxins

Identifiers

PMID40155776

What OpenQuestion holds

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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.