Distribution and Identification of Mycobacterium tuberculosis Lineage in Kashgar Prefecture

Abstract

Objectives In order to understand the composition of Mycobacterium tuberculosis(M.tb) lineage and find specific tags to distinguish lineage of the M.tb in Kashgar prefecture, so as to provide a basis for the prevention of tuberculosis in this area. Methods Whole genome sequencing (WGS) of M.tb clinical strains (161 cases) was conducted. The phylogenetic tree was constructed by Maximum Likelihood (ML) on the basis of single nucleotide polymorphisms (SNPs) and verified via principal component analysis (PCA). The composition structure of M.tb in different regions was analyzed by combining geographic information. Results The M.tb clinical strains were composed of lineage 2 (73/161, 45.34%), lineage 3 (52/161, 32.30%) and lineage 4 (36/161, 22.36%) in Kashgar prefecture. And the 3 lineages were subdivided into 11 sublineages, among which lineage 2 includes lineage 2.2.2/Asia Ancestral 1(9/73, 12.33%),lineage 2.2.1-Asia Ancestral 2(9/73, 12.33%)༌lineage 2.2.1-Asia Ancestral 3(18/73, 24.66%) and lineage 2.2.1-Modern Beijing(39/73, 53.42%).Lineage 3 includes lineage 3.2(14/52, 26.92%)and lineage 3.3(38/52, 73.08%)༌lineage 4 includes lineage 4.1(3/36, 8.33%)༌lineage 4.2(2/36, 5.66%)༌lineage 4.4.2(1/36, 2.78%)༌lineage 4.5(28/36, 77.78%) and lineage 4.8(2/36, 5.66%)༌all of which were consistent with the PCA results. Among the identified 21438 SNPs ,there are 136 markers proposed to discriminate known circulating strains. Reconstruction of a phylogenetic tree using the 136 SNPs for all 161 samples resulted in a tree with the same number of delineated clades. Based on geographical location analysis, the composition of Lineage 2 in Kashgar prefecture (45.34%) is lower than other regions level in China(54.35%-90.27%), and the composition of Lineage 3 (32.30%)is much higher than other regions level in China (0.92%-2.01%), but it is lower than the bordering Pakistan (70.40%). Conclusion In summary, M.tb clinical strains from Kashgar prefecture were identifed 3 lineages and 11 sublineages, with 136 Branch-Specific SNP. Kashgar borders countries with a high incidence of tuberculosis such as Pakistan and India, resulting in a large difference between the M.tb lineage and sublineage distribution in this region and other provinces in China. This research provides a theoretical basis for the prevention and control of tuberculosis in Xinjiang.