ArticleTuberculosis (Edinburgh, Scotland)2016
Serial image analysis of Mycobacterium tuberculosis colony growth reveals a persistent subpopulation in sputum during treatment of pulmonary TB.
Article in Tuberculosis (Edinburgh, Scotland), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Sputum lipoarabinomannan (LAM) as a biomarker to determine sputum mycobacterial load: exploratory and model-based analyses of integrated data from four cohorts.BMC infectious diseases · 2022Trial
- Quantification of bactericidal activity using the PATHFAST TB LAM Ag assay during the first 14 days of pulmonary tuberculosis treatment.Frontiers in antibiotics · 2025Article
- Bacterial colony size growth estimation by deep learning.BMC microbiology · 2023Article
- High rifampicin peak plasma concentrations accelerate the slow phase of bacterial decline in tuberculosis patients: Evidence for heteroresistance.PLoS computational biology · 2023Article
- Xpert Ultra testing of blood in severe HIV-associated tuberculosis to detect and measure Mycobacterium tuberculosis blood stream infection: a diagnostic and disease biomarker cohort study.The Lancet. Microbe · 2022Article
- Clinically encountered growth phenotypes of tuberculosis-causing bacilli and theirFrontiers in cellular and infection microbiology · 2022Review
- Improving the Drug Development Pipeline for Mycobacteria: Modelling Antibiotic Exposure in the Hollow Fibre Infection Model.Antibiotics (Basel, Switzerland) · 2021Review
- ODELAM: Rapid Sequence-independent Detection of Drug Resistance inBio-protocol · 2021Article
- Molecular reprogramming and phenotype switching inProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Mechanisms of Drug-Induced Tolerance in Mycobacterium tuberculosis.Clinical microbiology reviews · 2020Review
- Article
- Tolerance and Persistence to Drugs: A Main Challenge in the Fight AgainstFrontiers in microbiology · 2020Review
- Model-Based Relationship between the Molecular Bacterial Load Assay and Time to Positivity in Liquid Culture.Antimicrobial agents and chemotherapy · 2019Article
- Lipoarabinomannan in sputum to detect bacterial load and treatment response in patients with pulmonary tuberculosis: Analytic validation and evaluation in two cohorts.PLoS medicine · 2019Article
- Prolonged bacterial lag time results in small colony variants that represent a sub-population of persisters.Nature communications · 2018Article
- The importance of clinical pharmacokinetic-pharmacodynamic studies in unraveling the determinants of early and late tuberculosis outcomes.International journal of pharmacokinetics · 2017Review
- Metabolic Perspectives on Persistence.Microbiology spectrum · 2017Review
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Faster elimination of drug tolerant 'persister' bacteria may shorten treatment of tuberculosis (TB) but no method exists to quantify persisters in clinical samples. We used automated image analysis to assess whether studying growth characteristics of individual Mycobacterium tuberculosis colonies from sputum on solid media during early TB treatment facilitates 'persister' phenotyping. As Time to Detection (TTD) in liquid culture inversely correlates with total bacterial load we also evaluated the relationship between individual colony growth parameters and TTD. Sputum from TB patients in Malawi was prepared for solid and liquid culture after 0, 2 and 4 weeks of treatment. Serial photography of agar plates was used to measure time to appearance (lag time) and radial growth rate for each colony. Mixed-effects modelling was used to analyse changing growth characteristics from serial samples. 20 patients had colony measurements recorded at ≥1 time-point. Overall lag time increased by 6.5 days between baseline and two weeks (p = 0.0001). Total colony count/ml showed typical biphasic elimination, but long lag time colonies (>20days) had slower, monophasic decline. TTD was associated with minimum lag time (time to appearance of first colony1). Slower elimination of long lag time colonies suggests that these may represent a persister subpopulation of bacilli.
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