Mycobacterium tuberculosis (Mtb) lineage 1 (L1) contributes considerably to the disease morbidity. While whole genome sequencing (WGS) is increasingly used for studying Mtb, our understanding of genetic diversity of L1 remains limited. Using phylogenetic analysis of WGS data from endemic range in Asia and Africa, we provide an improved genotyping scheme for L1. Mapping deletion patterns of the 68 direct variable repeats (DVRs) in the CRISPR region of the genome onto the phylogeny provided supporting evidence that the CRISPR region evolves primarily by deletion, and hinted at a possible Southeast Asian origin of L1. Both phylogeny and DVR patterns clarified some relationships between different spoligotypes, and highlighted the limited resolution of spoligotyping. We identified a diverse repertoire of drug resistance mutations. Altogether, this study demonstrates the usefulness of WGS data for understanding the genetic diversity of L1, with implications for public health surveillance and TB control. It also highlights the need for more WGS studies in high-burden but underexplored regions.
Mycobacterium tuberculosis (Mtb) lineage 2 (L2) strains are present globally, contributing to a widespread tuberculosis (TB) burden, particularly in Asia where both prevalence of TB and numbers of drug resistant TB are highest. The increasing availability of whole-genome sequencing (WGS) data worldwide provides an opportunity to improve our understanding of the global genetic diversity of Mtb L2 and its association with the disease epidemiology and pathogenesis. However, existing L2 sublineage classification schemes leave >20 % of the Modern Beijing isolates unclassified. Here, we present a revised SNP-based classification scheme of L2 in a genomic framework based on phylogenetic analysis of >4000 L2 isolates from 34 countries in Asia, Eastern Europe, Oceania and Africa. Our scheme consists of over 30 genotypes, many of which have not been described before. In particular, we propose six main genotypes of Modern Beijing strains, denoted L2.2.M1–L2.2.M6. We also provide SNP markers for genotyping L2 strains from WGS data. This fine-scale genotyping scheme, which can classify >98 % of the studied isolates, serves as a basis for more effective monitoring and reporting of transmission and outbreaks, as well as improving genotype-phenotype associations such as disease severity and drug resistance. This article contains data hosted by Microreact.
Worldwide, studies investigating the relationship between the lineage of Mycobacterium tuberculosis (MTB) across geographic areas has empowered the “End TB” program and understand transmission across national boundaries. Genomic diversity of MTB varies with geographical locations and ethnicity. Genomic diversity can also affect the emergence of drug resistance. In Myanmar, we still have limited genetic information about geographical, ethnicity, and drug resistance linkage to MTB genetic information. This study aimed to describe the geno-spatial distribution of MTB and drug resistance profiles in Myanmar–Thailand border areas. A cross-sectional study was conducted with a total of 109 sequenced isolates. The lineages of MTB and the potential associated socio-demographic, geographic and clinical factors were analyzed using Fisher’s exact tests. p value of statistically significance was set at < 0.05. We found that 67% of the isolates were lineage 1 (L1)/East-African-Indian (EAI) (n = 73), followed by lineage 2 (L2)/Beijing (n = 26), lineage 4 (L4)/European American (n = 6) and lineage 3 (L3)/Delhi/Central Asian (n = 4). “Gender”, “type of TB patient”, “sputum smear grading” and “streptomycin resistance” were significantly different with the lineages of MTB. Sublineages of L1, which had never been reported elsewhere in Myanmar, were detected in this study area. Moreover, both ethnicity and lineage of MTB significantly differed in distribution by patient location. Diversity of the lineage of MTB and detection of new sublineages suggested that this small area had been resided by a heterogeneous population group who actively transmitted the disease. This information on distribution of lineage of MTB can be linked in the future with those on the other side of the border to evaluate cross-border transmission.
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