RESUMEN
Outbreak strains of Mycobacterium tuberculosis are promising candidates as targets in the search for intrinsic determinants of transmissibility, as they are responsible for many cases with sustained transmission; however, the use of low-resolution typing methods and restricted geographical investigations represent flaws in assessing the success of long-lived outbreak strains. We can now address the nature of outbreak strains by combining large genomic data sets and phylodynamic approaches. We retrospectively sequenced the whole genome of representative samples assigned to an outbreak circulating in the Canary Islands (the GC strain) since 1993, which accounts for ~20% of local tuberculosis cases. We selected a panel of specific single nucleotide polymorphism (SNP) markers for an in-silico search for additional outbreak-related sequences within publicly available tuberculosis genomic data. Using this information, we inferred the origin, spread, and epidemiological parameters of the GC strain. Our approach allowed us to accurately trace the historical and more recent dispersion of the GC strain. We provide evidence of a highly successful nature within the Canarian archipelago but limited expansion abroad. Estimation of epidemiological parameters from genomic data disagree with a distinctive biology of the GC strain. With the increasing availability of genomic data allowing for the accurate inference of strain spread and critical epidemiological parameters, we can now revisit the link between Mycobacterium tuberculosis genotypes and transmission, as is routinely carried out for SARS-CoV-2 variants of concern. We demonstrate that social determinants rather than intrinsically higher bacterial transmissibility better explain the success of the GC strain. Importantly, our approach can be used to trace and characterize strains of interest worldwide. IMPORTANCE Infectious disease outbreaks represent a significant problem for public health. Tracing outbreak expansion and understanding the main factors behind emergence and persistence remain critical to effective disease control. Our study allows researchers and public health authorities to use Whole-Genome Sequencing-based methods to trace outbreaks, and shows how available epidemiological information helps to evaluate the factors underpinning outbreak persistence. Taking advantage of all the freely available information placed in public repositories, researchers can accurately establish the expansion of an outbreak beyond original boundaries, and determine the potential risk of a strain to inform health authorities which, in turn, can define target strategies to mitigate expansion and persistence. Finally, we show the need to evaluate strain transmissibility in different geographic contexts to unequivocally associate spread to local or pathogenic factors, an important lesson taken from genomic surveillance of SARS-CoV-2.
RESUMEN
Transmission of Beijing Mycobacterium tuberculosis can be investigated based on genotypic analysis of clinical isolates. A Beijing strain began to spread on Gran Canaria Island, Spain, at the end of the last century. In 1996, only 3 years after its importation to the island, its frequency had increased to 27.1% of all the isolates. The strain was tracked during the following years, and the most recent data obtained corresponded to 2007-8, when its presence continued to be alarming (21%). In the current study, we updated data on the distribution of this strain 20 years (2013-2014) after it was first detected on the island and extended the analysis for the first time to all the mycobacteriology laboratories covering the population of the Canary Island archipelago. Rapid updating was enabled by means of 2 different strain-specific PCRs: one targeting a peculiar feature of the strain, which was identified based on an IS6110 copy mapping in the Rv2180c gene, and a newly defined strain-specific single nucleotide polymorphism, which was identified by whole-genome sequencing. The results showed that the strain has remained highly prevalent (20.90% of all isolates), has spread throughout the neighbouring islands, and has also reached high representativeness in them (11-32%).