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Lineage 2 (East Asian), which includes the Beijing genotype, is one of the most prevalent lineages of Mycobacterium tuberculosis (Mtb) throughout the world. The Beijing family is associated to hypervirulence and drug-resistant tuberculosis. The study of this genotype's circulation in Latin America is crucial for achieving total control of TB, the goal established by the World Health Organization, for the American sub-continent, before 2035. In this sense, the present work presents an overview of the status of the Beijing genotype for this region, with a bibliographical review, and data analysis of MIRU-VNTRs for available Beijing isolates. Certain countries present a prevalent trend of <5%, suggesting low transmissibility for the region, with the exception of Cuba (17.2%), Perú (16%) and Colombia (5%). Minimum Spanning Tree analysis, obtained from MIRU-VNTR data, shows distribution of specific clonal complex strains in each country. From this data, in most countries, we found that molecular epidemiology has not been a tool used for the control of TB, suggesting that the Beijing genotype may be underestimated in Latin America. It is recommended that countries with the highest incidence of the Beijing genotype use effective control strategies and increased care, as a requirement for public health systems.

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Tuberculosis continues to be an important public health problem. Particularly considering Beijingfamily strains of Mycobacterium tuberculosis, which have been associated with drug-resistance and hypervirulence. The Beijing-like SIT190 (BL) is the most prevalent Beijing strain in Colombia. The pathogenic mechanism and immune response against this pathogen is unknown. Thus, we compared the course of pulmonary TB in BALB/c mice infected with Classical-Beijing strain 391 and BL strain 323. The disease course was different among infected animals with Classical-Beijing and BL strain. Mice infected with BL had a 100% mortality at 45 days post-infection (dpi), with high bacillary loads and massive pneumonia, whereas infected animals with Classical-Beijing survived until 60 dpi and showed extensive pneumonia and necrosis. Lung RNA extraction was carried out at early (day 3 dpi), intermediate (day 14 dpi), and late (days 28 and 60 dpi) time points of infection. Transcriptional analysis of infected mice with Classical-Beijing showed several overexpressed genes, associated with a pro-inflammatory profile, including those for coding for CCL3 and CCL4 chemokines, both biomarkers of disease severity. Conversely, mice infected with BL displayed a profile which included the over-expression of several genes associated with immunesuppression, including Nkiras, Dleu2, and Sphk2, highlighting an anti-inflammatory milieu which would allow high bacterial replication followed by an intense inflammatory response. In summary, both Beijing strains induced a non-protective immune response which induced extensive tissue damage, BL strain induced rapidly extensive pneumonia and death, whereas Classical-Beijing strain produced slower extensive pneumonia later associated with extensive necrosis.

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