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- Title
Genetic investigation of isoniazid resistance in an ongoing tuberculosis outbreak in British Columbia.
- Authors
Hickey, Tyler B. M.; Tang, Patrick
- Abstract
OBJECTIVE: Beginning in 2008, an outbreak of tuberculosis (TB) that spread between two BC communities was identified. The Mycobacterium tuberculosis isolates were identical based on MIRU-VNTR genotyping. However, of the 20 cases of active TB identified, nine cases showed low level resistance to the antibiotic isoniazid (INH) whereas the others were fully susceptible to all first line anti-TB drugs. The M. tuberculosis from the index case acquired INH resistance during treatment in 2007 and the patient subsequently left hospital against medical advice. In order to understand the transmission dynamics within the outbreak and the evolution of INH resistance, we sought to determine the genetic mechanism of INH resistance. METHODS: Genomic DNA from the M. tuberculosis isolates was used for PCR and sequencing of several genes associated with INH resistance: katG, mabA, inhA, ndh, kasA, and oxyR-ahpC. The genetic sequences of the isolates were compared against one another, as well as against multiple reference sequences of M. tuberculosis. RESULTS: Sequence alignments of INH-susceptible and INH-resistant M. tuberculosis clinical isolates revealed identical sequences within the genes analyzed. In addition, there were no non-synonymous mutations between the sequences from the clinical isolates and those from reference strains known to INH-susceptible. CONCLUSIONS: We were unable to identify the mutation conferring INH resistance in this TB outbreak. Either the mutation is occurring in a gene that was not addressed in this study or there may exist a mixed population of both INH-resistant and INH-susceptible bacterial populations within individual patients in this outbreak group and the methods used in this study lacked the sensitivity to identify the INH-resistant populations. High throughput second generation sequencing is one methodology that may be able to address these limitations in future studies.
- Subjects
BRITISH Columbia; ISONIAZID; TUBERCULOSIS; DISEASE prevalence; MYCOBACTERIUM tuberculosis; DRUG resistance in microorganisms
- Publication
UBC Medical Journal, 2011, Vol 2, Issue 2, p14
- ISSN
1920-7425
- Publication type
Abstract