ArticleEBioMedicine2019
Direct transmission of within-host Mycobacterium tuberculosis diversity to secondary cases can lead to variable between-host heterogeneity without de novo mutation: A genomic investigation.
Article in EBioMedicine, 2019. 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, 24 citations in OpenAlex.
- Ecology, global diversity and evolutionary mechanisms in the Mycobacterium tuberculosis complex.Nature reviews. Microbiology · 2025Review
- Global epidemiology of Mycobacterium tuberculosis lineage 4 insights from Ecuadorian genomic data.Scientific reports · 2025Article
- A new method for detecting mixed Mycobacterium tuberculosis infection and reconstructing constituent strains provides insights into transmission.Genome medicine · 2025Article
- Within-host population dynamics of extensively drug-resistantEvolution, medicine, and public health · 2025Article
- A Genome-Focused Investigation Reveals the Emergence of aMicroorganisms · 2024Article
- Whole-Genome Sequencing Exhibits Better Diagnostic Performance than Variable-Number Tandem Repeats for Identifying Mixed Infections of Mycobacterium tuberculosis.Microbiology spectrum · 2023Article
- Genomic Sequencing Profiles ofTropical medicine and infectious disease · 2023Article
- Whole genome sequencing analysis to evaluate the influence of T2DM on polymorphisms associated with drug resistance in M. tuberculosis.BMC genomics · 2022Article
- Tuberculosis in Australia's tropical north: a population-based genomic epidemiological study.The Lancet regional health. Western Pacific · 2021Article
- The within-host evolution of antimicrobial resistance in Mycobacterium tuberculosis.FEMS microbiology reviews · 2021Review
- Mutation ofFrontiers in public health · 2021Article
- Review
- MycoVarP: Mycobacterium Variant and Drug Resistance Prediction Pipeline for Whole-Genome Sequence Data Analysis.Frontiers in bioinformatics · 2021Article
- Article
- Mechanisms of Drug-Induced Tolerance in Mycobacterium tuberculosis.Clinical microbiology reviews · 2020Review
- Contaminant DNA in bacterial sequencing experiments is a major source of false genetic variability.BMC biology · 2020Article
- Previously undetected super-spreading ofeLife · 2020Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundWhole genome sequencing (WGS) has enabled the development of new approaches to track Mycobacterium tuberculosis (Mtb) transmission between tuberculosis (TB) cases but its utility may be challenged by the discovery that Mtb diversifies within hosts. Nevertheless, there is limited data on the presence and degree of within-host evolution.
methodsWe profiled a well-documented Mtb transmission cluster with three pulmonary TB cases to investigate within-host evolution and describe its impact on recent transmission estimates. We used deep sequencing to track minority allele frequencies (<50·0% abundance) during transmission and standard treatment.
findingsPre-treatment (n = 3) and serial samples collected over 2 months of antibiotic treatment (n = 16) from all three cases were analysed. Consistent with the epidemiological data, zero fixed SNP separated all genomes. However, we identified six subclones between the three cases with an allele frequency ranging from 35·0% to 100·0% across sampling intervals. Five subclones were identified within the index case pre-treatment and shared with one secondary case, while only the dominant clone was observed in the other secondary case. By tracking the frequency of these heterogeneous alleles over the two-month therapy, we observed distinct signatures of drift and negative selection, but limited evidence for de novo mutations, even under drug pressure.
interpretationWe document within-host Mtb diversity in an index case, which led to transmission of minority alleles to a secondary case. Incorporating data on heterogeneous alleles may refine our understanding of Mtb transmission dynamics. However, more evidence is needed on the role of transmission bottleneck on observed heterogeneity between cases.
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