A novel Ancestral Beijing sublineage of Mycobacterium tuberculosis suggests the transition site to Modern Beijing sublineages.

Global Mycobacterium tuberculosis population comprises 7 major lineages. The Beijing strains, particularly the ones classified as Modern groups, have been found worldwide, frequently associated with drug resistance, younger ages, outbreaks and appear to be expanding. Here, we report analysis of whole genome sequences of 1170 M. tuberculosis isolates together with their patient profiles. Our samples belonged to Lineage 1-4 (L1-L4) with those of L1 and L2 being equally dominant. Phylogenetic analysis revealed several new or rare sublineages. Differential associations between sublineages of M. tuberculosis and patient profiles, including ages, ethnicity, HIV (human immunodeficiency virus) infection and drug resistance were demonstrated. The Ancestral Beijing strains and some sublineages of L4 were associated with ethnic minorities while L1 was more common in Thais. L2.2.1.Ancestral 4 surprisingly had a mutation that is typical of the Modern Beijing sublineages and was common in Akha and Lahu tribes who have migrated from Southern China in the last century. This may indicate that the evolutionary transition from the Ancestral to Modern Beijing sublineages might be gradual and occur in Southern China, where the presence of multiple ethnic groups might have allowed for the circulations of various co-evolving sublineages which ultimately lead to the emergence of the Modern Beijing strains.

Evidence for Host-Bacterial Co-evolution via Genome Sequence Analysis of 480 Thai Mycobacterium tuberculosis Lineage 1 Isolates.

Tuberculosis presents a global health challenge. Mycobacterium tuberculosis is divided into several lineages, each with a different geographical distribution. M. tuberculosis lineage 1 (L1) is common in the high-burden areas in East Africa and Southeast Asia. Although the founder effect contributes significantly to the phylogeographic profile, co-evolution between the host and M. tuberculosis may also play a role. Here, we reported the genomic analysis of 480 L1 isolates from patients in northern Thailand. The studied bacterial population was genetically diverse, allowing the identification of a total of 18 sublineages distributed into three major clades. The majority of isolates belonged to L1.1 followed by L1.2.1 and L1.2.2. Comparison of the single nucleotide variant (SNV) phylogenetic tree and the clades defined by spoligotyping revealed some monophyletic clades representing EAI2_MNL, EAI2_NTM and EAI6_BGD1 spoligotypes. Our work demonstrates that ambiguity in spoligotype assignment could be partially resolved if the entire DR region is investigated. Using the information to map L1 diversity across Southeast Asia highlighted differences in the dominant strain-types in each individual country, despite extensive interactions between populations over time. This finding supported the hypothesis that there is co-evolution between the bacteria and the host, and have implications for tuberculosis disease control.