Substantial molecular evolution in prolonged latent Mycobacterium tuberculosis infection in humans. M. tuberculosis re-activation study

With this study we provide an account of substantial molecular evolution in Mycobacterium tuberculosis overthree decades of latent infection in human hosts. Our findings are based on whole-genome sequencing of isolates from a unique Danish historical strain collection that dates back to the early 1920s. Thus far, related data on mycobacterial genome evolution during latency has been limited to animal studies, and over significantly shorter time-scales. Thus, in presenting this work, we provide insight into a much underreported aspect of M. tuberculosis biology, namely the mutational capacity during prolonged latency in humans. We report the accretion of mutations at rates similar to observations from cases of active disease. We provide a mechanistic insight into the underlying molecular processes, and show that either oxidative stress induced mutations or Darwinian evolution drives evolution during latency.