Substantial Molecular Evolution In Prolonged Latent Mycobacterium Tuberculosis Infections In Humans

Troels Lillebaek, Anders Norman, Erik Michael Rasmussen, Dorte B. Folkvardsen, Rasmus Marvig, Åse Bengaard Andersen, Lars Jelsbak

    Research output: Chapter in Book/Report/Conference proceedingConference abstract in proceedingsResearchpeer-review

    Abstract

    Introduction: Despite its central role as a reservoir for active tuberculosis disease (TB), latent Mycobacterium tuberculosis (Mtb) infections and the underlying persistence mechanisms are poorly understood. The Mtb genome in latently infected individuals may hold the key to understanding the processes that lead to reactivation and progression to clinical disease. Methods: We studied genomic relationships among 14 isolates of Mtb from historical and recent Danish clinical strain collections, spanning more than three decades, to investigate 6 putative cases of Mtb reactivation, inferred from IS6110 profiles. Single-nucleotide polymorphism (SNPs) patterns were analyzed to identify true cases of TB re-activation, as well as the underlying mutational patterns. Results: Two parallel cases of latent TB reactivation were identified. We found an average mutation rate of 0.2 – 0.3 over 33 years, as well as evidence for distinct processes such as oxidative damage or natural selection having contributed to mutation accumulation. Conclusions: Our study shows that distinct processes can shape Mtb genomes during latent infection. Most importantly, we document substantial molecular evolution of Mtb over three decades, with mutation rates similar to observations from cases of active disease. Our study thus emphasizes the importance of identifying and controlling latent cases.
    Original languageEnglish
    Title of host publicationThe Danish Microbiological Society Annual Congress 2015 : Programme & Abstracts
    Place of PublicationCopenhagen
    Publication date2015
    Pages50-50
    Publication statusPublished - 2015
    EventThe Danish Microbiological Society Annual Congress 2015 - Eigtved's Pakhus, Copenhagen, Denmark
    Duration: 9 Nov 20159 Nov 2015

    Conference

    ConferenceThe Danish Microbiological Society Annual Congress 2015
    LocationEigtved's Pakhus
    CountryDenmark
    CityCopenhagen
    Period09/11/201509/11/2015

    Cite this

    Lillebaek, T., Norman, A., Rasmussen, E. M., B. Folkvardsen, D., Marvig, R., Bengaard Andersen, Å., & Jelsbak, L. (2015). Substantial Molecular Evolution In Prolonged Latent Mycobacterium Tuberculosis Infections In Humans. In The Danish Microbiological Society Annual Congress 2015: Programme & Abstracts (pp. 50-50). Copenhagen.
    Lillebaek, Troels ; Norman, Anders ; Rasmussen, Erik Michael ; B. Folkvardsen, Dorte ; Marvig, Rasmus ; Bengaard Andersen, Åse ; Jelsbak, Lars. / Substantial Molecular Evolution In Prolonged Latent Mycobacterium Tuberculosis Infections In Humans. The Danish Microbiological Society Annual Congress 2015: Programme & Abstracts. Copenhagen, 2015. pp. 50-50
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    abstract = "Introduction: Despite its central role as a reservoir for active tuberculosis disease (TB), latent Mycobacterium tuberculosis (Mtb) infections and the underlying persistence mechanisms are poorly understood. The Mtb genome in latently infected individuals may hold the key to understanding the processes that lead to reactivation and progression to clinical disease. Methods: We studied genomic relationships among 14 isolates of Mtb from historical and recent Danish clinical strain collections, spanning more than three decades, to investigate 6 putative cases of Mtb reactivation, inferred from IS6110 profiles. Single-nucleotide polymorphism (SNPs) patterns were analyzed to identify true cases of TB re-activation, as well as the underlying mutational patterns. Results: Two parallel cases of latent TB reactivation were identified. We found an average mutation rate of 0.2 – 0.3 over 33 years, as well as evidence for distinct processes such as oxidative damage or natural selection having contributed to mutation accumulation. Conclusions: Our study shows that distinct processes can shape Mtb genomes during latent infection. Most importantly, we document substantial molecular evolution of Mtb over three decades, with mutation rates similar to observations from cases of active disease. Our study thus emphasizes the importance of identifying and controlling latent cases.",
    author = "Troels Lillebaek and Anders Norman and Rasmussen, {Erik Michael} and {B. Folkvardsen}, Dorte and Rasmus Marvig and {Bengaard Andersen}, {\AA}se and Lars Jelsbak",
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    Lillebaek, T, Norman, A, Rasmussen, EM, B. Folkvardsen, D, Marvig, R, Bengaard Andersen, Å & Jelsbak, L 2015, Substantial Molecular Evolution In Prolonged Latent Mycobacterium Tuberculosis Infections In Humans. in The Danish Microbiological Society Annual Congress 2015: Programme & Abstracts. Copenhagen, pp. 50-50, The Danish Microbiological Society Annual Congress 2015, Copenhagen, Denmark, 09/11/2015.

    Substantial Molecular Evolution In Prolonged Latent Mycobacterium Tuberculosis Infections In Humans. / Lillebaek, Troels; Norman, Anders; Rasmussen, Erik Michael; B. Folkvardsen, Dorte; Marvig, Rasmus; Bengaard Andersen, Åse; Jelsbak, Lars.

    The Danish Microbiological Society Annual Congress 2015: Programme & Abstracts. Copenhagen, 2015. p. 50-50.

    Research output: Chapter in Book/Report/Conference proceedingConference abstract in proceedingsResearchpeer-review

    TY - ABST

    T1 - Substantial Molecular Evolution In Prolonged Latent Mycobacterium Tuberculosis Infections In Humans

    AU - Lillebaek, Troels

    AU - Norman, Anders

    AU - Rasmussen, Erik Michael

    AU - B. Folkvardsen, Dorte

    AU - Marvig, Rasmus

    AU - Bengaard Andersen, Åse

    AU - Jelsbak, Lars

    PY - 2015

    Y1 - 2015

    N2 - Introduction: Despite its central role as a reservoir for active tuberculosis disease (TB), latent Mycobacterium tuberculosis (Mtb) infections and the underlying persistence mechanisms are poorly understood. The Mtb genome in latently infected individuals may hold the key to understanding the processes that lead to reactivation and progression to clinical disease. Methods: We studied genomic relationships among 14 isolates of Mtb from historical and recent Danish clinical strain collections, spanning more than three decades, to investigate 6 putative cases of Mtb reactivation, inferred from IS6110 profiles. Single-nucleotide polymorphism (SNPs) patterns were analyzed to identify true cases of TB re-activation, as well as the underlying mutational patterns. Results: Two parallel cases of latent TB reactivation were identified. We found an average mutation rate of 0.2 – 0.3 over 33 years, as well as evidence for distinct processes such as oxidative damage or natural selection having contributed to mutation accumulation. Conclusions: Our study shows that distinct processes can shape Mtb genomes during latent infection. Most importantly, we document substantial molecular evolution of Mtb over three decades, with mutation rates similar to observations from cases of active disease. Our study thus emphasizes the importance of identifying and controlling latent cases.

    AB - Introduction: Despite its central role as a reservoir for active tuberculosis disease (TB), latent Mycobacterium tuberculosis (Mtb) infections and the underlying persistence mechanisms are poorly understood. The Mtb genome in latently infected individuals may hold the key to understanding the processes that lead to reactivation and progression to clinical disease. Methods: We studied genomic relationships among 14 isolates of Mtb from historical and recent Danish clinical strain collections, spanning more than three decades, to investigate 6 putative cases of Mtb reactivation, inferred from IS6110 profiles. Single-nucleotide polymorphism (SNPs) patterns were analyzed to identify true cases of TB re-activation, as well as the underlying mutational patterns. Results: Two parallel cases of latent TB reactivation were identified. We found an average mutation rate of 0.2 – 0.3 over 33 years, as well as evidence for distinct processes such as oxidative damage or natural selection having contributed to mutation accumulation. Conclusions: Our study shows that distinct processes can shape Mtb genomes during latent infection. Most importantly, we document substantial molecular evolution of Mtb over three decades, with mutation rates similar to observations from cases of active disease. Our study thus emphasizes the importance of identifying and controlling latent cases.

    M3 - Conference abstract in proceedings

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    BT - The Danish Microbiological Society Annual Congress 2015

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    Lillebaek T, Norman A, Rasmussen EM, B. Folkvardsen D, Marvig R, Bengaard Andersen Å et al. Substantial Molecular Evolution In Prolonged Latent Mycobacterium Tuberculosis Infections In Humans. In The Danish Microbiological Society Annual Congress 2015: Programme & Abstracts. Copenhagen. 2015. p. 50-50