ArticlePLoS pathogens2022
Spatial relationships of intra-lesion heterogeneity in Mycobacterium tuberculosis microenvironment, replication status, and drug efficacy.
Article in PLoS pathogens, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 51 citations in OpenAlex.
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- Divergent Evolution of Tuberculosis Lesions During Treatment: A Longitudinal CT-Based Analysis of Progression and Regression Patterns.Diagnostics (Basel, Switzerland) · 2026Article
- Rv3839-Rv3840 links the endogenous heme biosynthesis pathway withbioRxiv : the preprint server for biology · 2026Article
- Serine/threonine protein kinase phosphorylation of DosR alters target gene transcription mechanics and regulates Mycobacterium tuberculosis response to nitric oxide stress.PLoS genetics · 2026Article
- In situ visualization of Clostridioides difficile phenotypic heterogeneity and single-cell morphology during gut infection.Nature communications · 2026Article
- Fundamental role of spatial positioning of Mycobacterium tuberculosis in mycobacterial survival in macrophages.Nature communications · 2025Article
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- Dysplastic lung repair fosters a tuberculosis-promoting microenvironment through maladaptive macrophage polarization.PLoS pathogens · 2025Article
- Incorporation of macrophage immune stresses into an intracellular assay of drug tolerance inAntimicrobial agents and chemotherapy · 2025Article
- Protocol for developing a mouse model of post-primary pulmonary tuberculosis after hematogenous spread in native lungs and lung implants.STAR protocols · 2025Article
- Increased proportion of growth-arrested bacilli in acidic pH adaptation promotesbioRxiv : the preprint server for biology · 2025Article
- How macrophage heterogeneity affects tuberculosis disease and therapy.Nature reviews. Immunology · 2025Review
- Cholesterol metabolism and intrabacterial potassium homeostasis are intrinsically related in Mycobacterium tuberculosis.PLoS pathogens · 2025Article
- Aberrant macrophage activation and maladaptive lung repair promote tuberculosis progression uniquely in the lung.bioRxiv : the preprint server for biology · 2025Article
- Building Spatiotemporal Understanding ofACS infectious diseases · 2025Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
A hallmark of Mycobacterium tuberculosis (Mtb) infection is the marked heterogeneity that exists, spanning lesion type differences to microenvironment changes as infection progresses. A mechanistic understanding of how this heterogeneity affects Mtb growth and treatment efficacy necessitates single bacterium level studies in the context of intact host tissue architecture; however, such an evaluation has been technically challenging. Here, we exploit fluorescent reporter Mtb strains and the C3HeB/FeJ murine model in an integrated imaging approach to study microenvironment heterogeneity within a single lesion in situ, and analyze how these differences relate to non-uniformity in Mtb replication state, activity, and drug efficacy. We show that the pH and chloride environments differ spatially even within a single caseous necrotic lesion, with increased acidity and chloride levels in the lesion cuff versus core. Strikingly, a higher percentage of Mtb in the lesion core versus cuff were in an actively replicating state, and correspondingly active in transcription/translation. Finally, examination of three first-line anti-tubercular drugs showed that isoniazid efficacy was conspicuously poor against Mtb in the lesion cuff. Our study reveals spatial relationships of intra-lesion heterogeneity, sheds light on important considerations in anti-tubercular treatment strategies, and establishes a foundational framework for Mtb infection heterogeneity analysis at the single bacterium level in situ.
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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.