Substantial molecular evolution and mutation rates in prolonged latent Mycobacterium tuberculosis infection in humans.
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.
International Reference Laboratory of Mycobacteriology, Statens Serum Institut, DK-2300 Copenhagen, Denmark. Electronic address: tll@ssi.dk.
Troels
T
Lillebaek
Department of Systems Biology, Technical University of Denmark, DK-2800 Lyngby, Denmark.
Anders
A
Norman
International Reference Laboratory of Mycobacteriology, Statens Serum Institut, DK-2300 Copenhagen, Denmark.
Erik Michael
EM
Rasmussen
Department of Systems Biology, Technical University of Denmark, DK-2800 Lyngby, Denmark.
Rasmus L
RL
Marvig
International Reference Laboratory of Mycobacteriology, Statens Serum Institut, DK-2300 Copenhagen, Denmark.
Dorte Bek
DB
Folkvardsen
Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, DK-2100 Copenhagen, Denmark.
Åse Bengård
ÅB
Andersen
Department of Systems Biology, Technical University of Denmark, DK-2800 Lyngby, Denmark. Electronic address: lj@bio.dtu.dk.
Lars
L
Jelsbak
D019143:Evolution, Molecular; D016680:Genome, Bacterial; D006801:Humans; D055985:Latent Tuberculosis / Q000382:microbiology*; D059645:Mutation Rate; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000302:isolation & purification*; D017422:Sequence Analysis, DNA
Genome sequencing; Latent infection; Mutation rate; Pathogen evolution; Within-host evolution