Evidence map›Paper›PMID 28781126›Full record

ArticleCell chemical biology2017

Targeting Mycobacterium tuberculosis Sensitivity to Thiol Stress at Acidic pH Kills the Bacterium and Potentiates Antibiotics.

Garry B Coulson, Benjamin K Johnson, Huiqing Zheng, Christopher J Colvin, Robert J Fillinger, Elizabeth R Haiderer, Neal D Hammer, Robert B Abramovitch

Open access · bronzeAbstract read
In one paragraph

Article in Cell chemical biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
4.2field-weighted citation impact, top 5% of its field
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

43 citing papers in PubMed, 67 citations in OpenAlex.

  1. Article
  2. Review
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  10. TowardMicroorganisms · 2024
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  16. TargetingMicrobiology (Reading, England) · 2024
    Review
  17. Article
  18. Structure of the SigE regulatory network inFrontiers in microbiology · 2024
    Article
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  20. SigE: A master regulator ofFrontiers in microbiology · 2023
    Review
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

8 authors at 1 institution in 1 country.

Garry B CoulsonDepartment of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
Benjamin K JohnsonDepartment of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
Huiqing ZhengDepartment of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
Christopher J ColvinDepartment of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
Robert J FillingerDepartment of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
Elizabeth R HaidererDepartment of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
Neal D HammerDepartment of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
Robert B AbramovitchDepartment of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA. Electronic address: abramov5@msu.edu.
Michigan State University · US

Funding

Treatments for Nipah Virus InfectionU54AI057159 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI ONDERDONK, ANDREW B. · 2003 to 2013
$113.7M
Vaccines and Therapies Against BotulismU54AI057153 · NIAID · UNIVERSITY OF CHICAGO · PI KANABROCKI, JOSEPH A. · 2003 to 2013
$87.6M
Mechanisms of Mycobacterium Tuberculosis pH-driven AdaptationR01AI116605 · NIAID · MICHIGAN STATE UNIVERSITY · PI ABRAMOVITCH, ROBERT B · 2016 to 2020
$1.9M
Screening for inhibitors of M. tuberculosis persistence-related lipid metabolismR21AI105867 · NIAID · MICHIGAN STATE UNIVERSITY · PI ABRAMOVITCH, ROBERT B · 2013 to 2014
$392k
NIAID NIH HHS R01 AI116605NIAID NIH HHS R21 AI105867NIAID NIH HHS U54 AI057153NIAID NIH HHS U54 AI057159
6 · The paper itself

Abstract

Mycobacterium tuberculosis (Mtb) must sense and adapt to immune pressures such as acidic pH during pathogenesis. The goal of this study was to isolate compounds that inhibit acidic pH resistance, thus defining virulence pathways that are vulnerable to chemotherapy. Here, we report that the compound AC2P36 selectively kills Mtb at acidic pH and potentiates the bactericidal activity of isoniazid, clofazimine, and diamide. We show that AC2P36 activity is associated with thiol stress and causes an enhanced accumulation of intracellular reactive oxygen species at acidic pH. Mechanism of action studies demonstrate that AC2P36 directly depletes Mtb thiol pools, with enhanced depletion of free thiols at acidic pH. These findings support that Mtb is especially vulnerable to thiol stress at acidic pH and that chemical depletion of thiol pools is a promising target to promote Mtb killing and potentiation of antimicrobials.

Indexed as

Anti-Bacterial AgentsBacterial ProteinsGlutathioneHydrogen-Ion ConcentrationMycobacterium tuberculosisOxidative StressPyrimidinesReactive Oxygen SpeciesSigma FactorStructure-Activity RelationshipSulfhydryl CompoundsSulfones5-chloro-N-(3-chloro-4-methoxyphenyl)-2-methylsulfonylpyrimidine-4-carboxamideAnti-Bacterial AgentsBacterial ProteinsGlutathionePyrimidinesReactive Oxygen SpeciesSigH protein, bacteriaSigma FactorSulfhydryl CompoundsSulfonesantibiotic potentiationchemical biologyenvironmental adaptationMycobacterium tuberculosisoxidative stressredox homeostasisthiol homeostasis

Identifiers

PMID28781126
PMCPMC5562523
OpenAlexW2745145358

What OpenQuestion holds

Textmetadata
LicenceTDM
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.