The bacterial pH gradient contributes to persistence in Mycobacterium tuberculosis
mBio·
- DOI
- 10.1128/mbio.01692-26
- PMID
- —
- PMCID
- —
- OpenAlex
- W7203700488
- Study type
- Journal article
- Publisher
- American Society for Microbiology
- Article type
- journal-article
- Integrity
- current
Why this research matters now
Findings suggest that pharmacological disruption of the bacterial pH gradient is a rapid chemical tool to study persister biology in TB, with potential broader relevance to other infectious diseases.
Structured evidence summary
Research question
The study investigates how chemical perturbation of the bacterial pH gradient and related proton motive force components influences drug-tolerant persistence in Mycobacterium tuberculosis.
Study design
A laboratory-based screening study using 2,336 FDA-approved drugs to identify compounds that modulate Mtb persistence, followed by targeted microbiological assays, transcriptomic profiling, and targeted gene knockdowns.
Population and setting
In vitro experimental work using Mycobacterium tuberculosis cultures; no human participants, clinical settings, or geographic field populations are described.
Main findings
Niclosamide protected Mtb against bactericidal doses of isoniazid, rifampicin, and other standard TB drugs. Disruption of the pH gradient with intracellular acidification, rather than disruption of membrane potential, was required to induce tolerance, and the protective effect was tunable by external pH. Transcriptomic analysis and knockdowns linked three Mtb-specific genes to either promoting or mitigating the tolerant state.
Public-health relevance
Findings suggest that pharmacological disruption of the bacterial pH gradient is a rapid chemical tool to study persister biology in TB, with potential broader relevance to other infectious diseases.
Important limitations
This summary is limited to the supplied single-article abstract and metadata; the original paper is required for decision-grade interpretation. The abstract does not explicitly state limitations of the study.
GIDS interpretation
The article is discoverable through TB- and treatment-related classifiers within GIDS; it provides context on laboratory models of Mtb drug tolerance and does not itself constitute a live surveillance signal.
Related GIDS surveillance
Literature context does not validate, explain, or change a surveillance signal. Exact and contextual relationships are shown separately.
Evidence relationships
This article has 6 auditable classifier relationships to diseases, places, topics, and study design.