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. 2013 Jul 18;369(3):290-2.
doi: 10.1056/NEJMc1215305.

Whole-genome sequencing for rapid susceptibility testing of M. tuberculosis

Claudio U Köser, Josephine M Bryant, Jennifer Becq, M Estée Török, Matthew J Ellington, Marc A Marti-Renom, Andrew J Carmichael, Julian Parkhill, Geoffrey P Smith, Sharon J Peacock

Whole-genome sequencing for rapid susceptibility testing of M. tuberculosis

Claudio U Köser et al. N Engl J Med. .
No abstract available

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Figures

Figure 1
Figure 1. Phylogenetic Analysis and the Distribution of Drug-Resistance Mutations
In Panel A, the numbers refer to the number of single-nucleotide polymorphisms (SNPs) that were shared by the two strains of extensively drug-resistant (XDR) Mycobacterium tuberculosis isolated from a single patient (termed majority and minority strains on the basis of numerical predominance) or were unique to one strain as compared with the M. tuberculosis H37Rv reference genome. The reference laboratory had reported resistance to nine antibiotics (black type). Genotypically, we found that both strains had mutations that were consistent with resistance to these nine drugs. The same mutation was present in both strains for six drugs (green overlap), but different mutations in each strain accounted for resistance to the remaining three drugs. Streptomycin is shown twice because both strains had a common resistance mutation, but the minority strain had a second resistance mutation. In addition, we found mutations that were associated with resistance to five antibiotics, for which no phenotypic results were available (red type). (Amithiozone is also known as thiacetazone.) Current genotypic tests could have detected only the nine antibiotic resistances marked by an asterisk (see Table S1 in the Supplementary Appendix). In Panel B, a phylogenetic tree based on whole-genome sequencing data shows the majority and minority strains from our patient as compared with data from a published study of XDR tuberculosis, which included representatives of the main lineages of M. tuberculosis and strains of M. africanum, M. orygis, M. bovis, and M. bovis bacillus Calmette-Guérin (BCG). For isolates in the Beijing lineage, the country of origin is shown after the name of the strain (London [L]; Samara Oblast, Russia [S], or Estonia [E]). The minority and majority XDR strains from our patient fell into clades A and B, respectively, of the Beijing lineage, which together account for 36% of Beijing cases in Samara. The closest relative of the majority strain was isolated in Estonia and is a representative of the dominant clone in this country. The results of mycobacterial inter spersed repetitive-unit-variable-number tandem-repeat genotyping of three samples from this patient were consistent with the majority strain (Table S2 in the Supplementary Appendix).
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