Genetic variation in Mycobacterium tuberculosis isolates from a London outbreak associated with isoniazid resistance

Giovanni Satta

Background: The largest outbreak of isoniazid-resistant (INH-R) Mycobacterium tuberculosis in Western Europe is centred in North London, with over 400 cases diagnosed since 1995.
In the current study we evaluated the genetic variation in a subset of outbreak clinical samples with the hypothesis that these isolates have unique biological characteristics that serve to prolong the outbreak.
Methods: Fitness assays, mutation rate and whole genome sequencing were performed to test for selective advantage and compensatory mutations.
Conclusions: This detailed analysis of the genetic variation of these INH-R samples suggests that this outbreak consists of successful, closely-related, circulating strains with heterogeneous resistance profiles and little or no associated fitness cost or impact on their mutation rate. Specific deletions and SNPs may be a peculiar feature of these isolates, which can potentially explain their persistence for years.

Simone Agnello
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