Evidence map›Paper›PMID 40760081›Full record

Articlenpj antimicrobials and resistance2025

The Parkinson's drug benztropine possesses histamine receptor 1-dependent host-directed antimicrobial activity against Mycobacterium tuberculosis.

Henok A Sahile, Matthew Christofferson, Morgan A Alford, Celine Rens, Hasti Haghdadi, Joseph D Chao, Georgia Langdon, Robert E W Hancock, Jeffrey Chen, Yossef Av-Gay

Abstract read
In one paragraph

Article in npj antimicrobials and resistance, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
–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 synthesis or guideline pooled it.

  1. Delayed-Type Hypersensitivity toInternational journal of molecular sciences · 2026
    Pooled it
  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

10 authors.

Henok A SahileDepartments of Medicine and Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada.
Matthew ChristoffersonDepartments of Medicine and Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada.
Morgan A AlfordCentre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, BC, Canada.
Celine RensDepartments of Medicine and Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada.
Hasti HaghdadiDepartments of Medicine and Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada.
Joseph D ChaoDepartments of Medicine and Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada.
Georgia LangdonDepartments of Medicine and Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada.
Robert E W HancockCentre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, BC, Canada.
Jeffrey ChenVaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK, Canada.
Yossef Av-GayDepartments of Medicine and Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada. yossi@mail.ubc.ca.

Funding

CIHR 152931CIHR 202305DI1
6 · The paper itself

Abstract

Intracellular pathogens such as Mycobacterium tuberculosis (Mtb) evade host defence mechanisms to infect and survive within host cells. Host-directed therapy (HDT) offers a promising alternative to antibiotics and may overcome antimicrobial resistance. Using high-content screening, we identified benztropine (BZT), an approved Parkinson's disease drug, as a potent inhibitor of intracellular Mtb. BZT is active in both human and murine macrophages but is inactive in broth. In an aerosol Mtb mouse infection model, oral administration of BZT reduced the burden of Mtb in the lungs by up to 70%. BZT was also active against Salmonella enterica serovar Typhimurium (STm) in an abscess model of infection, significantly reducing size and bacterial load. Chemical competition assays, CRISPR knockouts, and siRNA silencing assays revealed that BZT's activity against Mtb is mediated via macrophage histamine receptor 1 (HRH1). Our findings establish BZT as a promising repurposed candidate and a lead compound for developing HRH1-targeting antibacterial HDTs.

Identifiers

PMID40760081
PMCPMC12322000

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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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.