Substantial Molecular Evolution and Mutation Rates in Prolonged Latent Mycobacterium Tuberculosis Infection in Humans

Int J Med Microbiol. 2016 Nov;306(7):580-585. doi: 10.1016/j.ijmm.2016.05.017. Epub 2016 May 28.


The genome of Mycobacterium tuberculosis (Mtb) of latently infected individuals may hold the key to understanding the processes that lead to reactivation and progression to clinical disease. We report here analysis of pairs of Mtb isolates from putative prolonged latent TB cases. We identified two confirmed cases, and used whole genome sequencing to investigate the mutational processes that occur over decades in latent Mtb. We found an estimated mutation rate between 0.2 and 0.3 over 33 years, suggesting that latent Mtb accumulates mutations at rates similar to observations from cases of active disease.

Keywords: Genome sequencing; Latent infection; Mutation rate; Pathogen evolution; Within-host evolution.

MeSH terms

  • Evolution, Molecular*
  • Genome, Bacterial
  • Humans
  • Latent Tuberculosis / microbiology*
  • Mutation Rate*
  • Mycobacterium tuberculosis / genetics*
  • Mycobacterium tuberculosis / isolation & purification*
  • Sequence Analysis, DNA