Marked Microevolution of a Unique <i>Mycobacterium tuberculosis</i> Strain in 17 Years of Ongoing Transmission in a High Risk Population

<div><p>The transmission and persistence of <i>Mycobacterium tuberculosis</i> within high risk populations is a threat to tuberculosis (TB) control. In the current study, we used whole genome sequencing (WGS) to decipher the transmission dynamics and microevolution of <i>M. tuberculosis</i> ON-A, an endemic strain responsible for an ongoing outbreak of TB in an urban homeless/under-housed population. Sixty-one <i>M. tuberculosis</i> isolates representing 57 TB cases from 1997 to 2013 were subjected to WGS. Sequencing data was integrated with available epidemiological information and analyzed to determine how the <i>M. tuberculosis</i> ON-A strain has evolved during almost two decades of active transmission. WGS offers higher discriminatory power than traditional genotyping techniques, dividing the <i>M. tuberculosis</i> ON-A strain into 6 sub-clusters, each defined by unique single nucleotide polymorphism profiles. One sub-cluster, designated ON-A^NM (Natural Mutant; 26 isolates from 24 cases) was also defined by a large, 15 kb genomic deletion. WGS analysis reveals the existence of multiple transmission chains within the same population/setting. Our results help validate the utility of WGS as a powerful tool for identifying genomic changes and adaptation of <i>M. tuberculosis</i>.</p>