Use of whole genome sequencing to estimate the mutation rate of Mycobacterium tuberculosis during latent infection | Academic Article individual record
abstract

Tuberculosis poses a global health emergency, which has been compounded by the emergence of drug-resistant Mycobacterium tuberculosis (Mtb) strains. We used whole-genome sequencing to compare the accumulation of mutations in Mtb isolated from cynomolgus macaques with active, latent or reactivated disease. We sequenced 33 Mtb isolates from nine macaques with an average genome coverage of 93% and an average read depth of 117×. Based on the distribution of SNPs observed, we calculated the mutation rates for these disease states. We found a similar mutation rate during latency as during active disease or in a logarithmically growing culture over the same period of time. The pattern of polymorphisms suggests that the mutational burden in vivo is because of oxidative DNA damage. We show that Mtb continues to acquire mutations during disease latency, which may explain why isoniazid monotherapy for latent tuberculosis is a risk factor for the emergence of isoniazid resistance.

author list (cited authors)
Ford, C. B., Lin, P. L., Chase, M. R., Shah, R. R., Iartchouk, O., Galagan, J., ... Fortune, S. M.
publication date
2011
published in
keywords
  • Mycobacterium Tuberculosis
  • Mutation
  • Base Sequence
  • DNA, Bacterial
  • Humans
  • Models, Genetic
  • Genome, Bacterial
  • Polymorphism, Single Nucleotide
  • Drug Resistance, Bacterial
  • Antitubercular Agents
  • Macaca Fascicularis
  • Disease Models, Animal
  • Tuberculosis, Multidrug-Resistant
  • Latent Tuberculosis
  • Isoniazid
  • Animals
  • Time Factors
altmetric score

3.5

citation count

282