Genetic Diversity of the Mycobacterium tuberculosis Beijing Family Based on SNP and VNTR Typing Profiles in Asian Countries

Abstract

The Mycobacterium tuberculosis (MTB) Beijing strain is highly virulent, drug resistant, and endemic over Asia. To explore the genetic diversity of this family in several different regions of eastern Asia, 338 Beijing strains collected in Taiwan (Republic of China) were analyzed by mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing and compared with published MIRU-VNTR profiles and by the Hunter-Gaston diversity index (HGDI) of Beijing strains from Japan and South Korea. The results revealed that VNTR2163b (HGDI>0.6) and five other loci (VNTR424, VNTR4052, VNTR1955, VNTR4156 and VNTR 2996; HGDI>0.3) could be used to discriminate the Beijing strains in a given geographic region. Analysis based on the number of VNTR repeats showed three VNTRs (VNTR424, 3192, and 1955) to be phylogenetically informative loci. In addition, to determine the geographic variation of sequence types in MTB populations, we also compared sequence type (ST) data of our strains with published ST profiles of Beijing strains from Japan and Thailand. ST10, ST22, and ST19 were found to be prevalent in Taiwan (82%) and Thailand (92%). Furthermore, classification of Beijing sublineages as ancient or modern in Taiwan was found to depend on the repeat number of VNTR424. Finally, phylogenetic relationships of MTB isolates in Taiwan, South Korea, and Japan were revealed by a minimum spanning tree based on MIRU-VNTR genotyping. In this topology, the MIRU-VNTR genotypes of the respective clusters were tightly correlated to other genotypic characters. These results are consistent with the hypothesis that clonal evolution of these MTB lineages has occurred.

Genetic Diversity and Dynamic Distribution of Mycobacterium tuberculosis Isolates Causing Pulmonary and Extrapulmonary Tuberculosis in Thailand

“…The close historical relationship between China (39) and Japan (17) might be responsible for the BJ sublineages in Thailand. The most frequently identified strains in Taiwan were similar to predominant BJ subtypes in our populations, including ST10 (35.42%), ST19 (29.65%), and ST22 (13.46%) (40). Advanced means of global travel could affect the spread of infectious strains among countries, and bacterial adaptation raises concern over transnational transmission.…”

Association between genotype and drug resistance profiles of Mycobacterium tuberculosis strains circulating in China in a national drug resistance survey

“…One possible underlying reason is that Beijing lineage in China originated in the North, while the Euro American lineage originated in the South. Previous studies reported that the high genetic diversity of Beijing genotypes in Japan is consistent with their likely origin in this region, indicating a more ancient common ancestor for the Beijing genotype strains in North-Eastern Asia [27,28]. Conversely, some studies have detected Beijing (like) strains with a full spoligotyping pattern and a RD105 deletion or “extended” RD105 deletion in Southwest of China, which would be consistent with the common ancestor of the currently expanding Beijing strains originating from this region [23,29].…”

Molecular Epidemiology of Tuberculosis in Kaohsiung City Located at Southern Taiwan, 2000-2008

“…It is still the leading cause of death among all communicable infectious diseases despite a steady decline in both incidence and mortality rates since 1950. Previous studies indicate that the most prevalent Mycobacterium tuberculosis (MTB) strains in Taiwan belong to the Beijing lineage, followed by East African-Indian (EAI) and Haarlem strains [ 2 , 3 ]. Notably, EAI strains in northern Taiwan comprise about 11% of MTB isolates, whereas in southern Taiwan they comprise up to 32% [ 4 , 5 ].…”