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

Ajawatanawong, Pravech; Yanai, Hideki; Smittipat, Nat; Disratthakit, Areeya; Yamada, Norio; Miyahara, Reiko; Nedsuwan, Supalert; Imasanguan, Worarat; Kantipong, Pacharee; Chaiyasirinroje, Boonchai; Wongyai, Jiraporn; Plitphonganphim, Supada; Tantivitayakul, Pornpen; Phelan, Jody; Parkhill, Julian; Clark, Taane G.; Hibberd, Martin L.; Ruangchai, Wuthiwat; Palittapongarnpim, P; Juthayothin, Tada; Thawornwattana, Yuttapong; Viratyosin, Wasna; Tongsima, Sissades; Mahasirimongkol, Surakameth; Tokunaga, Katsushi; Palittapongarnpim, Prasit

doi:10.1038/s41598-019-50078-3

Cited by 53 publications

(92 citation statements)

References 51 publications

(99 reference statements)

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“…Therefore, as a southern province of China, Guangxi has more proportion of Ancestral Beijing strains and genetic diversity of Mtb strains than that in northern region [24]. The origin of Protobeijing strain (L 2.1) is likely to be in Southern China as it has the highest percentage [16]. In this study, the lineage 4 with three sub-lineages (L4.2, L4.4 and L4.5) also accounted for a large proportion.…”

Section: Resultsmentioning

confidence: 99%

The geno-spatio analysis of Mycobacterium tuberculosis complex in hot and cold spots of Guangxi, China

Lin

Cui

Virasakdi

et al. 2020

Preprint

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Abstract Background At present, there are few studies on polymorphism of Mycobacterium tuberculosis (Mtb) gene and how it affects the TB epidemic. This study aimed to document the differences of polymorphisms between tuberculosis hot and cold spot areas of Guangxi Zhuang Autonomous Region, China. Methods The cold and hot spot areas, each with 3 counties, had been pre-identified by TB incidence for 5 years from the surveillance database. Whole genome sequencing analysis was performed on all sputum Mtb isolates from the detected cases during January and June 2018. Single nucleotide polymorphism (SNP) of each isolate compared to the H37Rv strain were called and used for lineage and sub-lineage identification. Pairwise SNP differences between every pair of isolates were computed. Analyses of Molecular Variance (AMOVA) across counties of the same hot or cold spot area and between the two areas were performed. Results As a whole, 59.8% (57.7% sub-lineage 2.2 and 2.1% sub-lineage 2.1) and 39.8% (17.8% sub-lineage 4.4, 6.5% sub-lineage 4.2 and 15.5% sub-lineage 4.5) of the Mtb strains were Lineage 2 and Lineage 4 respectively. The percentages of sub-lineage 2.2 (Beijing family strains) are significantly higher in hot spots. Through the MDS dimension reduction, the genomic population structure in the three hot spot counties is significantly different from those three cold spot counties (T-test p = 0.05). The median of SNPs distances among Mtb isolates in cold spots was greater than that in hot spots (897 vs 746, Rank-sum test p < 0.001). Three genomic clusters, each with genomic distance ≤ 12 SNPs, were identified with 2, 3 and 4 consanguineous strains. Two clusters were from hot spots and one was from cold spots. Conclusion Narrower genotype diversity in the hot area may indicate higher transmissibility of the Mtb strains in the area compared to those in the cold spot area.

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Section: Resultsmentioning

confidence: 99%

The geno-spatio analysis of Mycobacterium tuberculosis complex in hot and cold spots of Guangxi, China

Lin

Cui

Virasakdi

et al. 2020

Preprint

Self Cite

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“…WGS analyses of two isolates (One SIT190/MDR and one SIT1/drug susceptible) confirmed the "modern" Beijing sublineage. Although, we only have the data for two out of the 37 Beijing strains, both strains shared all the 72 and 44 SNPs with the 2.2.1 "modern" sublineage of Beijing (S2 Table) mostly identified from China, Russia and Thailand [10,48]. These additional genetic descriptions revealed great similarity of the Beijing strains isolated in Colombia with "modern" Beijing strains from Asia instead of the Pacific or Asian-African Beijing sublineages [48].…”

Section: Plos Onementioning

confidence: 91%

“…Although, we only have the data for two out of the 37 Beijing strains, both strains shared all the 72 and 44 SNPs with the 2.2.1 "modern" sublineage of Beijing (S2 Table) mostly identified from China, Russia and Thailand [10,48]. These additional genetic descriptions revealed great similarity of the Beijing strains isolated in Colombia with "modern" Beijing strains from Asia instead of the Pacific or Asian-African Beijing sublineages [48]. Additionally, our MDR strain that was sequenced shared the eight SNPs that were proposed to be exclusively present in Beijing MDR strains from Colombia (Table 4) [35].…”

Section: Plos Onementioning

confidence: 99%

Genetic profiling of Mycobacterium tuberculosis revealed “modern” Beijing strains linked to MDR-TB from Southwestern Colombia

et al. 2020

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Beijing strains of Mycobacterium tuberculosis (lineage 2) have been associated with drug-resistance and transmission of tuberculosis worldwide. Most of the Beijing strains identified in the Colombian Pacific coast have exhibited a multidrug resistant (MDR) phenotype. We sought to evaluate the clonality and sublineage of Beijing strains circulating in Southwestern Colombia. Thirty-seven Beijing strains were identified through spoligotyping out of 311 clinical isolates collected in 9 years from 2002-2010. Further analysis by MIRU-VNTR 24 loci was conducted for the Beijing strains. For sublineage classification, deletions of RD105, RD207, and RD131 and point mutations at fbpB, mutT2, and acs were evaluated. Drug-resistance associated mutations to first-and second-line anti-TB drugs were also evaluated. Additionally, two Beijing strains were Illumina-whole genome sequenced (one MDR and one drug-susceptible). Among the 37 Beijing strains characterized, 36 belonged to the SIT190 type from which 28 were MDR, four pre-extensively drug resistant (XDR) TB, and four XDR-TB. The remaining strain was SIT1 and drug susceptible. MIRU-VNTR analysis allowed the identification of three Beijing clusters and two unique strains. Beijing strains were confirmed as "modern" sublineage. The mutations rpoB S531L and katG S315T were the most common among MDR strains. Moreover, the two strains evaluated by whole genome sequencing (WGS) shared most of the genetic features with the sublineage 2.2.1 "modern" Beijing previously characterized from Asian strains. WGS analysis of the MDR strain revealed the presence of eight SNPs previously reported in other MDR "Beijing-like" strains from Colombia. The presence of "modern" Beijing strains in Southwestern Colombia, most of them with MDR phenotype, suggests a different origin of this M. tuberculosis sublineage compared to other Beijing strains found in neighboring South American countries. This work may serve as a genetic baseline to

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“…Comparison of demographic characteristics and area of residence (cold vs hot area) was done using Pearson's chi-square test for categorical variables and the ranksum test for continuous variables. Molecular typing and statistical inference were conducted based on the genotype assignment of the isolates based on the SNP classi cation [16]. Analysis of Molecular Variance (AMOVA) was used to test the genomic differentiation (F-statistic index) between the groups [17].…”

Section: Statistical Analysesmentioning

confidence: 99%

Interaction analysis of Mycobacterium tuberculosis between host environment and highly mutated genes from population genetic structure comparison

Cui

Lin

Chang

et al. 2020

Preprint

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Objective We aimed to investigate the genetic and demographic differences and interactions between areas where observed genomic variations in Mycobacterium tuberculosis (M. Tb) are distributed uniformly in cold and hot spots. Methods The cold and hot spot areas were identified using the reported incidence of TB over the previous 5 years. Whole genome sequencing was performed on 291 M. tb isolates between January and June 2018. Analysis of molecular variance (AMOVA) and a multifactor dimensionality reduction (MDR) model was applied to test gene-gene-environment interactions. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were computed to test the extent to which genetic mutation affects the TB epidemic using a multivariate logistic regression model. Results The percentage of the Beijing family strain in hot spots was significantly higher than that in cold spots (64.63% vs 50.69%, p = 0.022), among elderly, people with a low BMI and those having a history of contact with a TB patient (all p < 0.05). Individuals from cold spot areas had a higher frequency of out-of-town travelling (p < 0.05). The mutation of Rv1186c, Rv3900c, Rv1508c, Rv0210 and a Intergenic Region (SNP site: 3847237) showed a significant difference between cold and hot spots. (p < 0.001). The MDR model displayed a clear negative interaction effect of age groups with BMI (interaction entropy: -3.55%) and mutation of Rv0210 (interaction entropy: -2.39%). Through the mutations of Rv0210 and BMI had a low independent effect (interaction entropy: -1.46%). Conclusion Our data suggests a statistical significant role of age, BMI and the polymorphisms of Rv0210 genes in the transmission and development of M. tb. The results provide clues for the study of susceptibility genes of M. tb in different population.

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

Cited by 53 publications

References 51 publications

The geno-spatio analysis of Mycobacterium tuberculosis complex in hot and cold spots of Guangxi, China

The geno-spatio analysis of Mycobacterium tuberculosis complex in hot and cold spots of Guangxi, China

Genetic profiling of Mycobacterium tuberculosis revealed “modern” Beijing strains linked to MDR-TB from Southwestern Colombia

Interaction analysis of Mycobacterium tuberculosis between host environment and highly mutated genes from population genetic structure comparison

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