New Mycobacterium tuberculosis Beijing clonal complexes in China revealed by phylogenetic and Bayesian population structure analyses of 24-loci MIRU-VNTRs

Abstract

Beijing lineage of Mycobacterium tuberculosis constitutes the most predominant lineage in East Asia. Beijing epidemiology, evolutionary history, genetics are studied in details for years revealing probable origin from China followed by worldwide expansion, partially linked to higher mutation rate, hypervirulence, drug-resistance, and association with cases of mixed infections. Considering huge amount of data available for 24-loci Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats, we performed detailed phylogenetic and Bayesian population structure analyses of Beijing lineage strains in mainland China and Taiwan using available 24-loci MIRU-VNTR data extracted from publications or the SITVIT2 database (n = 1490). Results on genetic structuration were compared to previously published data. A total of three new Beijing clonal complexes tentatively named BSP1, BPS2 and BSP3 were revealed with surprising phylogeographical specificities to previously unstudied regions in Sichuan, Chongqing and Taiwan, proving the need for continued investigations with extended datasets. Such geographical restriction could correspond to local adaptation of these “ecological specialist” Beijing isolates to local human host populations in contrast with “generalist pathogens” able to adapt to several human populations and to spread worldwide.

Local adaptive evolution of two distinct clades of Beijing and T families of Mycobacterium tuberculosis in Chongqing: a Bayesian population structure and phylogenetic study

“…The study was based on genotyping and geographical distribution data of a collection of MTB isolates (n = 16 090) from China. These data were mainly collected from the published literatures (n = 15 830), and there were also a small collection from a key laboratory of Sichuan University (n = 193) [13] and the SITVIT2 database (http://www.pasteur-guadeloupe.fr:8081/SIT-VIT) (n = 67), respectively [19] (Supplementary Table 1). In the collected data, spoligotype international types (SIT) information of 12 674 isolates was available and listed (Supplementary Table 2), and the 24-loci MIRU-VNTR data of 2161 isolates amongst all the data collected were available (Supplementary Table 3).…”

“…Several recent studies suggested that the Bayesian population structure analysis method based on the 24loci mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) could divide each family of MTB into more detailed clades [11][12][13]. The global T family was divided into eight T sub-lineage (TSL1-TSL8) by Bayesian population structure analysis [12], while the Beijing family in China into five Beijing sub-pedigree (BSP1-BSP5) [13].…”

“…Several recent studies suggested that the Bayesian population structure analysis method based on the 24loci mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) could divide each family of MTB into more detailed clades [11][12][13]. The global T family was divided into eight T sub-lineage (TSL1-TSL8) by Bayesian population structure analysis [12], while the Beijing family in China into five Beijing sub-pedigree (BSP1-BSP5) [13]. Interestingly, the clade distribution varies substantially with regions, especially for BSP2 and TSL6, since 99.49% of BSP2 and 89.79% of TSL6 isolates are distributed in Chongqing, compared with that only 0.51% of BSP2 isolates were in Xinjiang, and 4.08, 2.04 and 2.04% of TSL6 in Guizhou, Sichuan, and Jiangsu province, respectively [12,13].…”

“…The global T family was divided into eight T sub-lineage (TSL1-TSL8) by Bayesian population structure analysis [12], while the Beijing family in China into five Beijing sub-pedigree (BSP1-BSP5) [13]. Interestingly, the clade distribution varies substantially with regions, especially for BSP2 and TSL6, since 99.49% of BSP2 and 89.79% of TSL6 isolates are distributed in Chongqing, compared with that only 0.51% of BSP2 isolates were in Xinjiang, and 4.08, 2.04 and 2.04% of TSL6 in Guizhou, Sichuan, and Jiangsu province, respectively [12,13].…”

“…In order to clarify whether BSP2 and TSL6 originated by their local adaptive evolution from the specific clades of Beijing and T families in Chongqing, the genotyping data of 16 090 MTB isolates from laboratory collection in China, published literatures and an open database [19] were collected (Supplementary Table 1). The Bayesian population structure analysis was implemented to mold the consistent clades [12,13]. The Spacer Oligonucleotide Forest (Spoligoforest) analysis and the 24-loci MIRU-VNTR-based minimum spanning tree (MST) analysis were used to explore the phylogenetic pathways of different families and their clades [20,21] (Fig.…”