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- Title
Use of Whole Genome Sequencing to Determine the Microevolution of <i>Mycobacterium tuberculosis</i> during an Outbreak.
- Authors
Kato-Maeda, Midori; Ho, Christine; Passarelli, Ben; Banaei, Niaz; Grinsdale, Jennifer; Flores, Laura; Anderson, Jillian; Murray, Megan; Rose, Graham; Kawamura, L. Masae; Pourmand, Nader; Tariq, Muhammad A.; Gagneux, Sebastien; Hopewell, Philip C.
- Abstract
Rationale: Current tools available to study the molecular epidemiology of tuberculosis do not provide information about the directionality and sequence of transmission for tuberculosis cases occurring over a short period of time, such as during an outbreak. Recently, whole genome sequencing has been used to study molecular epidemiology of Mycobacterium tuberculosis over short time periods. Objective: To describe the microevolution of M. tuberculosis during an outbreak caused by one drug-susceptible strain. Method and Measurements: We included 9 patients with tuberculosis diagnosed during a period of 22 months, from a population-based study of the molecular epidemiology in San Francisco. Whole genome sequencing was performed using Illumina’s sequencing by synthesis technology. A custom program written in Python was used to determine single nucleotide polymorphisms which were confirmed by PCR product Sanger sequencing. Main results: We obtained an average of 95.7% (94.1–96.9%) coverage for each isolate and an average fold read depth of 73 (1 to 250). We found 7 single nucleotide polymorphisms among the 9 isolates. The single nucleotide polymorphisms data confirmed all except one known epidemiological link. The outbreak strain resulted in 5 bacterial variants originating from the index case A1 with 0–2 mutations per transmission event that resulted in a secondary case. Conclusions: Whole genome sequencing analysis from a recent outbreak of tuberculosis enabled us to identify microevolutionary events observable during transmission, to determine 0–2 single nucleotide polymorphisms per transmission event that resulted in a secondary case, and to identify new epidemiologic links in the chain of transmission.
- Subjects
TUBERCULOSIS transmission; NUCLEOTIDE sequence; TUBERCULOSIS diagnosis; BACTERIAL evolution; MYCOBACTERIUM tuberculosis; BACTERIAL genomes; MOLECULAR epidemiology; BACTERIOLOGY
- Publication
PLoS ONE, 2013, Vol 8, Issue 3, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0058235