ArticleMicrobiology (Reading, England)2016
Elucidating population-wide mycobacterial replication dynamics at the single-cell level.
Article in Microbiology (Reading, England), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 71 citations in OpenAlex.
- Bacterial strategies for surviving antibiotics during urinary tract infection: could uropathogenic Escherichia coli be persisters?Nature reviews. Urology · 2026Review
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- Proteomic insights into a M. tuberculosis clinical isolate with an increased propensity to form viable but non-replicating subpopulations during acid stress.Scientific reports · 2026Article
- Beyond culturability: VBNC-like and differentially culturableFrontiers in cellular and infection microbiology · 2026Review
- Building Spatiotemporal Understanding ofACS infectious diseases · 2025Review
- Persistence phenotype of adherent-invasiveMicrobial cell (Graz, Austria) · 2025Article
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- A prophage competition element protects Salmonella from lysis.Cell host & microbe · 2024Article
- Assessing the propensity of TB clinical isolates to form viable but non-replicating subpopulations.Scientific reports · 2024Article
- Novel Populations ofMicroorganisms · 2024Article
- Tracking the progeny of bacterial persisters using a CRISPR-based genomic recorder.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Host stress drives tolerance and persistence: The bane of anti-microbial therapeutics.Cell host & microbe · 2024Review
- Altered serine metabolism promotes drug tolerance inAntimicrobial agents and chemotherapy · 2024Article
- Droplet based whole genome amplification for sequencing minute amounts of purified Mycobacterium tuberculosis DNA.Scientific reports · 2024Article
- Intoxication of antibiotic persisters by host RNS inactivates their efflux machinery during infection.PLoS pathogens · 2024Article
- Quantification of Mycobacterium tuberculosis Growth in Cell-Based Infection Assays by Time-Lapse Fluorescence Microscopy.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Identification of genes associated with persistence inFrontiers in microbiology · 2024Article
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- Investigating Mycobacterium tuberculosis sufR (rv1460) in vitro and ex vivo expression and immunogenicity.PloS one · 2023Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Mycobacterium tuberculosis infections result in a spectrum of clinical outcomes, and frequently the infection persists in a latent, clinically asymptomatic state. The within-host bacterial population is likely to be heterogeneous, and it is thought that persistent mycobacteria arise from a small population of viable, but non-replicating (VBNR) cells. These are likely to be antibiotic tolerant and necessitate prolonged treatment. Little is known about these persistent mycobacteria, since they are very difficult to isolate. To address this, we have successfully developed a replication reporter system for use in M. tuberculosis. This approach, termed fluorescence dilution, exploits two fluorescent reporters; a constitutive reporter allows the tracking of bacteria, while an inducible reporter enables the measurement of bacterial replication. The application of fluorescence single-cell analysis to characterize intracellular M. tuberculosis identified a distinct subpopulation of non-growing mycobacteria in murine macrophages. The presence of VBNR and actively replicating mycobacteria was observed within the same macrophage after 48 h of infection. Furthermore, our results suggest that macrophage uptake resulted in enrichment of non- or slowly replicating bacteria (as revealed by d-cycloserine treatment); this population is likely to be highly enriched for persisters, based on its drug-tolerant phenotype. These results demonstrate the successful application of the novel dual fluorescence reporter system both in vitro and in macrophage infection models to provide a window into mycobacterial population heterogeneity.
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Registered trials
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