Resolving a clinical tuberculosis outbreak using palaeogenomic genome reconstruction methodologies

Rhys Jones, Marcela Sandoval Velasco, Llinos G. Harris, Sue Morgan, Mark Temple, Michael C. Ruddy, Rhian Williams, Michael D. Perry, Matt Hitchings, Thomas S. Wilkinson, Thomas Humphrey, M. Thomas P. Gilbert, Angharad P. Davies*

*Corresponding author for this work

    Abstract

    This study describes the analysis of DNA from heat-killed (boilate) isolates of Mycobacterium tuberculosis from two UK outbreaks where DNA was of sub-optimal quality for the standard methodologies routinely used in microbial genomics. An Illumina library construction method developed for sequencing ancient DNA was successfully used to obtain whole genome sequences, allowing analysis of the outbreak by gene-by-gene MLST, SNP mapping and phylogenetic analysis. All cases were spoligotyped to the same Haarlem H1 sub-lineage. This is the first described application of ancient DNA library construction protocols to allow whole genome sequencing of a clinical tuberculosis outbreak. Using this method it is possible to obtain epidemiologically meaningful data even when DNA is of insufficient quality for standard methods.

    Original languageEnglish
    Article number101865
    JournalTuberculosis
    Volume119
    Number of pages5
    ISSN1472-9792
    DOIs
    Publication statusPublished - Dec 2019

    Keywords

    • Ancient DNA library construction
    • Mycobacterium tuberculosis
    • Outbreak investigation
    • Palaeogenomics
    • Whole genome sequencing

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