Use of whole genome sequencing to estimate the mutation rate of Mycobacterium tuberculosis during latent infection
| Autor: | Christopher B. Ford, Nilofar Mohaideen, Marc Lipsitch, Rupal R. Shah, Philana Ling Lin, JoAnne L. Flynn, Sarah M. Fortune, James E. Galagan, Oleg Iartchouk, James C. Sacchettini, Thomas R. Ioerger, Michael R. Chase |
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| Rok vydání: | 2011 |
| Předmět: |
DNA
Bacterial Mutation rate Time Factors Tuberculosis Antitubercular Agents Single-nucleotide polymorphism Biology medicine.disease_cause Polymorphism Single Nucleotide Article Mycobacterium tuberculosis 03 medical and health sciences Latent Tuberculosis Drug Resistance Bacterial Tuberculosis Multidrug-Resistant Isoniazid Genetics medicine Animals Humans 030304 developmental biology Whole genome sequencing 0303 health sciences Mutation Base Sequence Models Genetic Latent tuberculosis 030306 microbiology respiratory system bacterial infections and mycoses medicine.disease biology.organism_classification Virology 3. Good health Disease Models Animal Macaca fascicularis Genome Bacterial medicine.drug |
| Zdroj: | Nature genetics |
| ISSN: | 1546-1718 1061-4036 |
| Popis: | Mycobacterium tuberculosis (Mtb) has generated a global health catastrophe that has been compounded by the emergence of drug resistant Mtb strains. We used whole genome sequencing to compare the accumulation of mutations in Mtb isolated from cynomolgus macaques with active, latent and reactivated disease. Based on the distribution of SNPs observed, we calculated the mutation rates for these disease states. Our data suggest that Mtb acquires a similar number of chromosomal mutations during latency as occurs during active disease or in a logarithmically growing culture over the same period of time despite reduced bacterial replication during latent infection. The pattern of polymorphisms suggests that the mutational burden in vivo is due to oxidative DNA damage. Thus, we demonstrate that Mtb continues to acquire mutations during latency and provide a novel explanation for the observation that isoniazid monotherapy for latent tuberculosis is a risk factor for the emergence of INH resistance1,2. |
| Databáze: | OpenAIRE |
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