32 results on '"Jia-Ru Chang"'
Search Results
2. Activation of M1 Macrophages in Response to Recombinant TB Vaccines With Enhanced Antimycobacterial Activity
- Author
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Shiu-Ju Yang, Yih-Yuan Chen, Chih-Hao Hsu, Chia-Wei Hsu, Chun-Yu Chang, Jia-Ru Chang, and Horng-Yunn Dou
- Subjects
recombinant Bacille Calmette–Guérin ,Mycobacterium tuberculosis ,innate immunity ,macrophage ,vaccine ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Pulmonary tuberculosis (TB) is a difficult-to-eliminate disease. Although the Bacille Calmette–Guérin (BCG) vaccine against Mycobacterium tuberculosis (MTB) has been available for decades, its efficacy is variable and has lessened over time. Furthermore, the BCG vaccine no longer protects against newly emerged Beijing strains which are responsible for many current infections in adults. Development of a novel vaccine is urgently needed. In this study, we first tested the efficacy of our recombinant BCG vaccines rBCG1 and rBCG2, compared to parental BCG, against MTB strain H37Ra in mice. Both the bacterial load and the level of lymphocyte infiltration decreased dramatically in the three groups treated with vaccine, especially rBCG1 and rBCG2. Furthermore, the Th1 and Th17 responses increased and macrophage numbers rose in the vaccination groups. Th1-mediated production of cytokines TNF-α, IFN-γ, and MCP-1 as well as M1-polarized cells all increased in lung tissue of the rBCG1 and rBCG2 groups. Clodronate-induced depletion of macrophages reduced the level of protection. Based on these results, we conclude that rBCG vaccines induce a significant increase in the number of M1 macrophages, which augments their potential as TB vaccine candidates.
- Published
- 2020
- Full Text
- View/download PDF
3. Genetic diversity of the Mycobacterium tuberculosis East AfricanâIndian family in three tropical Asian countries
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Yih-Yuan Chen, Jia-Ru Chang, Wei-Feng Huang, Chih-Hao Hsu, Han-Yin Cheng, Jun-Ren Sun, Shu-Chen Kuo, Ih-Jen Su, Ming-Shian Lin, Wei Chen, and Horng-Yunn Dou
- Subjects
Microbiology ,QR1-502 - Abstract
Background: The Beijing lineage of Mycobacterium tuberculosis (MTB) is the most predominant MTB strain in Asian countries and is spreading worldwide, however, the East AfricanâIndian (EAI) lineage is also particularly prevalent in many tropical Asian countries. The evolutionary relationships among MTB EAI isolates from Taiwan and those of tropical Asian countries remain unknown. Methods: The EAI strains collected from patients in Taiwan were analyzed using spacer oligonucleotide typing and mycobacterial interspersed repetitive unitâvariable number of tandem repeats (MIRU-VNTR) typing, and compared with published profiles from Cambodia and Singapore to investigate potential epidemiological linkages. Results: Among the three countries, the EAI lineage was most prevalent in Cambodia (60%; Singapore, 25.62%; and Taiwan, 21.85%), having also the highest rates of multidrug resistance and lowest rates of clustering of MTB isolates. We describe a convenient method using seven selected MIRU-VNTR loci for first-line typing to discriminate Beijing and EAI lineages. A potential epidemiological linkage in these tropical Asian countries is also discussed based on a minimum-spanning tree constructed using 24 MIRU-VNTR loci of MTB EAI strains. Conclusion: This study identified evolutionary relationships among MTB EAI isolates from Taiwan and those of two other tropical Asian countries, Cambodia and Singapore. Keywords: East AfricanâIndian family, Mycobacterium tuberculosis, tropical Asian countries
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- 2017
- Full Text
- View/download PDF
4. Combining molecular typing and spatial pattern analysis to identify areas of high tuberculosis transmission in a moderate-incidence county in Taiwan
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Yih-Yuan Chen, Jia-Ru Chang, Chih-Da Wu, Yen-Po Yeh, Shiu-Ju Yang, Chih-Hao Hsu, Ming-Ching Lin, Ching-Fang Tsai, Ming-Shian Lin, Ih-Jen Su, and Horng-Yunn Dou
- Subjects
Medicine ,Science - Abstract
Abstract In total, 303 randomly selected clinical Mycobacterium tuberculosis (MTB) isolates from 303 patients (collected January to December 2012) in central Taiwan were examined. The major lineages found were Beijing (N = 114, 37.62%), Haarlem (N = 76, 25.08%) and East African–Indian (EAI) (N = 42, 13.86%). Notably, younger persons (≤30 years old) were 6.58 times more likely to be infected with a Beijing genotype compared to older persons (>70 years) (p
- Published
- 2017
- Full Text
- View/download PDF
5. Lineage-specific SNPs for genotyping of Mycobacterium tuberculosis clinical isolates
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Horng-Yunn Dou, Chien-Hsing Lin, Yih-Yuan Chen, Shiu-Ju Yang, Jia-Ru Chang, Keh-Ming Wu, Ying-Tsong Chen, Pei-Ju Chin, Yen-Ming Liu, Ih-Jen Su, and Shih-Feng Tsai
- Subjects
Medicine ,Science - Abstract
Abstract Tuberculosis (TB) is a severe infectious disease worldwide. Genetic variation of the causative agent, Mycobacterium tuberculosis (MTB), determines the outcomes of infection and anti-TB treatment. Until recently, there has been no effective and convenient way for classifying clinical isolates based on the DNA sequences of the divergent lineages of MTB infecting human populations. Here, we identified single nucleotide polymorphisms (SNPs) of six representative strains from Taiwan by whole-genome sequencing and comparing the results to the sequence of the H37Rv reference strain. One hundred and ten SNPs, each unique to one of the six strains, were used to genotype 150 additional isolates by applying DNA mass spectrometry. Lineage-specific SNPs were identified that could distinguish the major lineages of the clinical isolates. A subset including 32 SNPs was found to be sufficient to type four major groups of MTB isolates in Taiwan (ancient Beijing, modern Beijing, East African–Indian, and Latin-American Mediterranean). However, there was high genetic homozygosity within the Euro-American lineage, which included spoligotype-classified Haarlem and T strains. By whole-genome sequencing of 12 representative Euro-American isolates, we identified multiple subtype-specific SNPs which allowed us to distinguish two major branches within the Euro-American lineage.
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- 2017
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6. Genomics Study of Mycobacterium tuberculosis Strains from Different Ethnic Populations in Taiwan
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Horng-Yunn Dou, Yih-Yuan Chen, Ying-Tsong Chen, Jia-Ru Chang, Chien-Hsing Lin, Keh-Ming Wu, Ming-Shian Lin, Ih-Jen Su, and Shih-Feng Tsai
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Evolution ,QH359-425 - Published
- 2016
7. Genomics Study of Strains from Different Ethnic Populations in Taiwan
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Horng-Yunn Dou, Yin-Yuan Chen, Ying-Tsong Chen, Jia-Ru Chang, Chien-Hsing Lin, Ken-Ming Wu, Ming-Shian Lin, Ih-Jen Su, and Shih-Feng Tsai
- Subjects
Evolution ,QH359-425 - Abstract
To better understand the transmission and evolution of Mycobacterium tuberculosis (MTB) in Taiwan, six different MTB isolates (representatives of the Beijing ancient sublineage, Beijing modern sublineage, Haarlem, East-African Indian, T1, and Latin-American Mediterranean (LAM)) were characterized and their genomes were sequenced. Discriminating among large sequence polymorphisms (LSPs) that occur once versus those that occur repeatedly in a genomic region may help to elucidate the biological roles of LSPs and to identify the useful phylogenetic relationships. In contrast to our previous LSP-based phylogeny, the sequencing data allowed us to determine actual genetic distances and to define precisely the phylogenetic relationships between the main lineages of the MTB complex. Comparative genomics analyses revealed more nonsynonymous substitutions than synonymous changes in the coding sequences. Furthermore, MTB isolate M7, a LAM-3 clinical strain isolated from a patient of Taiwanese aboriginal origin, is closely related to F11 (LAM), an epidemic tuberculosis strain isolated in the Western Cape of South Africa. The PE/PPE protein family showed a higher dn/ds ratio compared to that for all protein-coding genes. Finally, we found Haarlem-3 and LAM-3 isolates to be circulating in the aboriginal community in Taiwan, suggesting that they may have originated with post-Columbus Europeans. Taken together, our results revealed an interesting association with historical migrations of different ethnic populations, thus providing a good model to explore the global evolution and spread of MTB.
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- 2016
- Full Text
- View/download PDF
8. Molecular epidemiology of tuberculosis in Kaohsiung City located at southern Taiwan, 2000-2008.
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Yih-Yuan Chen, Jia-Ru Chang, Shu-Chen Kuo, Fan-Chen Tseng, Wei-Chen Huang, Tsi-Shu Huang, Yao-Shen Chen, Tzong-Shi Chiueh, Jun-Ren Sun, Ih-Jen Su, and Horng-Yunn Dou
- Subjects
Medicine ,Science - Abstract
BACKGROUND:We present the first comprehensive analysis of Mycobacterium tuberculosis (MTB) isolates circulating in southern Taiwan. In this 9-year population-based study, the TB situation in the Kaohsiung region was characterized by genotypic analysis of 421 MTB isolates. METHODS:All 421 isolates of MTB were analyzed by spoligotyping and MIRU-VNTR typing. Drug-resistance patterns were also analyzed. RESULTS:The percentage of EAI (East African-Indian) strains increased across sampling years (2000-2008) in southern Taiwan, whereas the proportion of Beijing lineages remained unchanged. Clustering was more frequent with EAI genotype infections (odds ratio = 3.6, p
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- 2015
- Full Text
- View/download PDF
9. Distinct modes of transmission of tuberculosis in aboriginal and non-aboriginal populations in Taiwan.
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Yih-Yuan Chen, Fan-Chen Tseng, Jia-Ru Chang, Shu-Chen Kuo, Jen-Jyh Lee, Jun-Jun Yeh, Tzong-Shi Chiueh, Jun-Ren Sun, Ih-Jen Su, and Horng-Yunn Dou
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Medicine ,Science - Abstract
Tuberculosis incidence among aborigines is significantly higher than for Han Chinese in Taiwan, but the extent to which Mycobacterium tuberculosis (MTB) strain characteristics contribute to this difference is not well understood. MTB isolates from aborigines and Han Chinese living in eastern and southern Taiwan, the major regions of aborigines, were analyzed by spoligotyping and 24-loci MIRU-VNTR. In eastern Taiwan, 60% of aboriginal patients were ≤20 years old, significantly younger than the non-aboriginal patients there; aborigines were more likely to have clustered MTB isolates than Han Chinese (odds ratio (OR) = 5.98, p
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- 2014
- Full Text
- View/download PDF
10. The pattern of cytokine production in vitro induced by ancient and modern Beijing Mycobacterium tuberculosis strains.
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Yih-Yuan Chen, Jia-Ru Chang, Wei-Feng Huang, Shu-Ching Hsu, Shu-Chen Kuo, Jun-Ren Sun, and Horng-Yunn Dou
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Medicine ,Science - Abstract
It is unclear to what extent the host-responses elicited by Beijing versus non-Beijing strains of Mycobacterium tuberculosis (MTB) contribute to the predominance of modern Beijing strains in Taiwan and some other Asian countries. The purpose of this study was to compare the expression profiles of virulence-related genes in human monocyte-derived macrophages infected in vitro with Beijing (ancient and modern strains) and non-Beijing strains (EAI strains) of MTB that are epidemic in Taiwan. We found that modern Beijing strains induced lower levels of pro-inflammatory cytokines, whereas EAI strains induced higher levels. Notably, the most prevalent modern Beijing sub-lineage, possessing intact RD150 and RD142 chromosomal regions, induced very low levels of pro-inflammatory cytokines, especially interleukin-1β. Moreover, in an intracellular growth assay, the survival of the same modern Beijing strain in human monocyte-derived macrophages was significantly higher than that of an ancient Beijing strain and an EAI strain. Taken together, these results may explain why modern Beijing strains of MTB predominate in Taiwan.
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- 2014
- Full Text
- View/download PDF
11. Clonal expansion of both modern and ancient genotypes of Mycobacterium tuberculosis in southern Taiwan.
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Jia-Ru Chang, Yih-Yuan Chen, Tsi-Shu Huang, Wei-Feng Huang, Shu-Chen Kuo, Fan-Chen Tseng, Ih-Jen Su, Chien-Hsing Lin, Yao-Shen Chen, Jun-Ren Sun, Tzong-Shi Chiueh, and Horng-Yunn Dou
- Subjects
Medicine ,Science - Abstract
We present the first comprehensive analysis of Mycobacterium tuberculosis isolates circulating in the Kaohsiung region of southern Taiwan. The major spoligotypes found in the 224 isolates studied were Beijing lineages (n = 97; 43.3%), EAI lineages (n = 72; 32.1%) and Haarlem lineages (n = 18; 8.0%). By 24 MIRU-VNTR typing, 174 patterns were identified, including 24 clusters of 74 isolates and 150 unique patterns. The combination of spoligotyping and 12-MIRU-VNTR revealed that 129 (57.6%) of the 224 isolates were clustered in 18 genotypes. Moreover, 63.6% (7/11) of infected persons younger than 30 years had a Beijing strain, which could suggest recent spread among younger persons by this family of TB strains in Kaohsiung. Among the 94 Beijing family (SIT1, SIT250 and SIT1674) isolates further analyzed for SNPs by mass spectrometry, the most frequent strain found was ST10 (n = 49; 52%), followed by ST22 (n = 17; 18%) and ST19 (n = 11; 12%). Among the EAI-Manila family isolates analyzed by region deletion-based subtyping, the most frequent strain found was RD type 1 (n = 63; 87.5%), followed by RD type 2 (n = 9; 12.5%). In our previous study, the proportion of modern Beijing strains (52.5%) in northern Taiwan was significantly higher than the proportion of EAI strains (11%). In contrast, in the present study, EAI strains comprised up to 32% of Beijing strains in southern Taiwan. In conclusion, both 'modern' (Beijing) and 'ancient' (EAI) M. tuberculosis strains are prevalent in the Kaohsiung region, perhaps suggesting that both strains are somehow more adapted to southern Taiwan. It will be interesting to investigate the dynamics of the lineage composition by different selection pressures.
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- 2012
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12. Genetic diversity of the Mycobacterium tuberculosis Beijing family based on SNP and VNTR typing profiles in Asian countries.
- Author
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Yih-Yuan Chen, Jia-Ru Chang, Wei-Feng Huang, Shu-Chen Kuo, Ih-Jen Su, Jun-Ren Sun, Tzong-Shi Chiueh, Tsi-Shu Huang, Yao-Shen Chen, and Horng-Yunn Dou
- Subjects
Medicine ,Science - 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.
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- 2012
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13. Rapid molecular diagnosis of live Mycobacterium tuberculosis on an integrated microfluidic system
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Chih-Hung Wang, Jia-Ru Chang, Shang-Cheng Hung, Horng-Yunn Dou, and Gwo-Bin Lee
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Materials Chemistry ,Metals and Alloys ,Electrical and Electronic Engineering ,Condensed Matter Physics ,Instrumentation ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials - Published
- 2022
14. Corrigendum: Activation of M1 Macrophages in Response to Recombinant TB Vaccines With Enhanced Antimycobacterial Activity
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Jia-Ru Chang, Yih-Yuan Chen, Shiu-Ju Yang, Chih-Hao Hsu, Chia-Wei Hsu, Horng-Yunn Dou, and Chun-Yu Chang
- Subjects
medicine.drug_class ,Immunology ,Disease ,macrophage ,Antimycobacterial ,law.invention ,Mycobacterium tuberculosis ,law ,vaccine ,Immunology and Allergy ,Medicine ,Macrophage ,innate immunity ,Original Research ,Innate immune system ,biology ,business.industry ,RC581-607 ,biology.organism_classification ,Vaccination ,Recombinant DNA ,recombinant Bacille Calmette–Guérin ,Immunologic diseases. Allergy ,business ,BCG vaccine - Abstract
Pulmonary tuberculosis (TB) is a difficult-to-eliminate disease. Although the Bacille Calmette-Guerin (BCG) vaccine against Mycobacterium tuberculosis (MTB) has been available for decades, its efficacy is variable and has lessened over time. Furthermore, the BCG vaccine no longer protects against newly emerged Beijing strains which are responsible for many current infections in adults. Development of a novel vaccine is urgently needed. In this study, we first tested the efficacy of our recombinant BCG vaccines rBCG1 and rBCG2, compared to parental BCG, against MTB strain H37Ra in mice. Both the bacterial load and the level of lymphocyte infiltration decreased dramatically in the three groups treated with vaccine, especially rBCG1 and rBCG2. Furthermore, the Th1 and Th17 responses increased and macrophage numbers rose in the vaccination groups. Th1-mediated production of cytokines TNF-α, IFN-γ, and MCP-1 as well as M1-polarized cells all increased in lung tissue of the rBCG1 and rBCG2 groups. Clodronate-induced depletion of macrophages reduced the level of protection. Based on these results, we conclude that rBCG vaccines induce a significant increase in the number of M1 macrophages, which augments their potential as TB vaccine candidates.
- Published
- 2021
15. Genetic diversity of the Mycobacterium tuberculosis East AfricanâIndian family in three tropical Asian countries
- Author
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Jun-Ren Sun, Jia-Ru Chang, Wei Chen, Horng-Yunn Dou, Ih-Jen Su, Wei-Feng Huang, Ming-Shian Lin, Chih-Hao Hsu, Han-Yin Cheng, Shu-Chen Kuo, and Yih-Yuan Chen
- Subjects
0301 basic medicine ,Microbiology (medical) ,DNA, Bacterial ,Genetic Markers ,Lineage (evolution) ,030106 microbiology ,Taiwan ,lcsh:QR1-502 ,Microbial Sensitivity Tests ,lcsh:Microbiology ,Mycobacterium tuberculosis ,03 medical and health sciences ,Spacer Oligonucleotide Typing ,Tandem repeat ,Asian People ,Immunology and Microbiology(all) ,Asian country ,Immunology and Allergy ,Humans ,Typing ,Tuberculosis, Pulmonary ,Genetics ,Genetic diversity ,Singapore ,General Immunology and Microbiology ,biology ,Traditional medicine ,Strain (biology) ,Genetic Variation ,General Medicine ,biology.organism_classification ,bacterial infections and mycoses ,Interspersed Repetitive Sequences ,Molecular Typing ,030104 developmental biology ,Infectious Diseases ,East African–Indian family ,DNA, Intergenic ,tropical Asian countries ,Cambodia - Abstract
Background: The Beijing lineage of Mycobacterium tuberculosis (MTB) is the most predominant MTB strain in Asian countries and is spreading worldwide, however, the East AfricanâIndian (EAI) lineage is also particularly prevalent in many tropical Asian countries. The evolutionary relationships among MTB EAI isolates from Taiwan and those of tropical Asian countries remain unknown. Methods: The EAI strains collected from patients in Taiwan were analyzed using spacer oligonucleotide typing and mycobacterial interspersed repetitive unitâvariable number of tandem repeats (MIRU-VNTR) typing, and compared with published profiles from Cambodia and Singapore to investigate potential epidemiological linkages. Results: Among the three countries, the EAI lineage was most prevalent in Cambodia (60%; Singapore, 25.62%; and Taiwan, 21.85%), having also the highest rates of multidrug resistance and lowest rates of clustering of MTB isolates. We describe a convenient method using seven selected MIRU-VNTR loci for first-line typing to discriminate Beijing and EAI lineages. A potential epidemiological linkage in these tropical Asian countries is also discussed based on a minimum-spanning tree constructed using 24 MIRU-VNTR loci of MTB EAI strains. Conclusion: This study identified evolutionary relationships among MTB EAI isolates from Taiwan and those of two other tropical Asian countries, Cambodia and Singapore. Keywords: East AfricanâIndian family, Mycobacterium tuberculosis, tropical Asian countries
- Published
- 2017
16. Recombinant bacille Calmette–Guerin coexpressing Ag85b, CFP10, and interleukin-12 elicits effective protection against Mycobacterium tuberculosis
- Author
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Jia-Ru Chang, Wei-Feng Huang, Chih-Wei Lin, Ih-Jen Su, Shu-Ching Hsu, Han-Yin Cheng, Horng-Yunn Dou, Chih-Hao Hsu, and Yih-Yuan Chen
- Subjects
0301 basic medicine ,Enzyme-Linked Immunospot Assay ,Interferon ,vaccine ,Immunology and Allergy ,Tuberculosis Vaccines ,Lung ,recombinant bacille Calmette–Guerin ,Mice, Inbred C3H ,Vaccines, Synthetic ,biology ,Interleukin ,General Medicine ,Interleukin-12 ,Mycobacterium bovis ,Human morbidity ,Vaccination ,Infectious Diseases ,Interleukin 12 ,Female ,medicine.drug ,Microbiology (medical) ,Tuberculosis ,030106 microbiology ,Peripheral blood mononuclear cell ,Mycobacterium tuberculosis ,Interferon-gamma ,03 medical and health sciences ,Adjuvants, Immunologic ,Bacterial Proteins ,Immunology and Microbiology(all) ,medicine ,Animals ,Humans ,Antigens, Bacterial ,General Immunology and Microbiology ,Tumor Necrosis Factor-alpha ,business.industry ,Macrophages ,Th1 Cells ,medicine.disease ,biology.organism_classification ,Virology ,Mice, Inbred C57BL ,030104 developmental biology ,Immunology ,Leukocytes, Mononuclear ,business ,Acyltransferases ,Spleen - Abstract
Background The tuberculosis (TB) pandemic remains a leading cause of human morbidity and mortality, despite widespread use of the only licensed anti-TB vaccine, bacille Calmette-Guerin (BCG). The protective efficacy of BCG in preventing pulmonary TB is highly variable; therefore, an effective new vaccine is urgently required. Methods In the present study, we assessed the ability of novel recombinant BCG vaccine (rBCG) against Mycobacterium tuberculosis by using modern immunological methods. Results Enzyme-linked immunospot assays demonstrated that the rBCG vaccine, which coexpresses two mycobacterial antigens (Ag85B and CFP10) and human interleukin (IL)-12 (rBCG2) elicits greater interferon-γ (IFN-γ) release in the mouse lung and spleen, compared to the parental BCG. In addition, rBCG2 triggers a Th1-polarized response. Our results also showed that rBCG2 vaccination significantly limits M. tuberculosis H37Rv multiplication in macrophages. The rBCG2 vaccine surprisingly induces significantly higher tumor necrosis factor-α (TNF-α) production by peripheral blood mononuclear cells that were exposed to a nonmycobacterial stimulus, compared to the parental BCG. Conclusion In this study, we demonstrated that the novel rBCG2 vaccine may be a promising candidate vaccine against M. tuberculosis infection.
- Published
- 2017
17. An integrated microfluidic system for identification of live mycobacterium tuberculosis by real-time polymerase chain reaction
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Horng-Yunn Dou, Ting-Hang Liu, Jia-Ru Chang, Ka-U Ip, and Gwo-Bin Lee
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Materials science ,biology ,Pcr cloning ,010402 general chemistry ,Molecular diagnostics ,biology.organism_classification ,01 natural sciences ,Virology ,0104 chemical sciences ,law.invention ,Mycobacterium tuberculosis ,03 medical and health sciences ,0302 clinical medicine ,Real-time polymerase chain reaction ,Colony formation ,Propidium monoazide ,law ,030212 general & internal medicine ,Tb treatment ,Polymerase chain reaction - Abstract
Mycobacterium tuberculosis (TB) infection poses a huge challenge worldwide. It is challenging for rapid identification of TB due to its low growth rate, and therefore it could be widely spread. For this reason, a novel combination of propidium monoazide (PMA) and real-time polymerase chain reaction (RT-PCR) was reported in this work for fast detection of live TB. Experimental results showed that the PMA-RT-PCR protocol can detect live TB with a detection limit as low as 14 colony formation units (CFU)/reaction by measuring the threshold cycle number (Ct value) in a calibration curve. Furthermore, PMA could be used successfully to distinguish dead TB such that no PCR products could be generated. More importantly, all the procedure could be finished within 2 hours. This is the first time that an integrated microfluidic system was demonstrated to use molecular diagnostics for fast detection of TB and could be potentially used for prognosis monitoring of TB treatment.
- Published
- 2018
18. Combining molecular typing and spatial pattern analysis to identify areas of high tuberculosis transmission in a moderate-incidence county in Taiwan
- Author
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Shiu Ju Yang, Yih Yuan Chen, Ching Fang Tsai, Yen Po Yeh, Horng Yunn Dou, Chih-Hao Hsu, Jia Ru Chang, Ih-Jen Su, Ming Ching Lin, Chih Da Wu, and Ming Shian Lin
- Subjects
Adult ,Male ,0301 basic medicine ,Tuberculosis ,Science ,030106 microbiology ,Taiwan ,Minisatellite Repeats ,Population density ,Article ,Mycobacterium tuberculosis ,03 medical and health sciences ,Molecular typing ,Beijing ,Risk Factors ,medicine ,Humans ,Typing ,Tuberculosis, Pulmonary ,Aged ,Retrospective Studies ,Population Density ,Multidisciplinary ,biology ,Incidence ,Age Factors ,Retrospective cohort study ,Middle Aged ,biology.organism_classification ,medicine.disease ,Bacterial Typing Techniques ,Increased risk ,Geographic Information Systems ,Medicine ,Female ,Environmental Monitoring ,Demography - Abstract
In total, 303 randomly selected clinical Mycobacterium tuberculosis (MTB) isolates from 303 patients (collected January to December 2012) in central Taiwan were examined. The major lineages found were Beijing (N = 114, 37.62%), Haarlem (N = 76, 25.08%) and East African–Indian (EAI) (N = 42, 13.86%). Notably, younger persons (≤30 years old) were 6.58 times more likely to be infected with a Beijing genotype compared to older persons (>70 years) (p
- Published
- 2017
19. Molecular epidemiology of Mycobacterium tuberculosis in aboriginal peoples of Taiwan, 2006–2011
- Author
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Jia-Ru Chang, Jun-Ren Sun, Jen-Jyh Lee, Wei-Feng Huang, Tzong-Shi Chiueh, Shu-Chen Kuo, Chang-Sheng Jang, Ih-Jen Su, Yih-Yuan Chen, Horng-Yunn Dou, and Jun-Jun Yeh
- Subjects
Adult ,Male ,Microbiology (medical) ,Tuberculosis ,Genotype ,Southern taiwan ,Taiwan ,Mycobacterium tuberculosis ,Young Adult ,Asian People ,medicine ,Humans ,Typing ,Aged ,Retrospective Studies ,Aged, 80 and over ,Molecular Epidemiology ,High prevalence ,Molecular epidemiology ,biology ,Traditional medicine ,Transmission (medicine) ,business.industry ,Incidence (epidemiology) ,Genetic Variation ,Middle Aged ,biology.organism_classification ,medicine.disease ,Molecular Typing ,Infectious Diseases ,Female ,business ,Demography - Abstract
Summary Previous research revealed a 6-fold higher incidence of tuberculosis (TB) amongst aborigines compared to Han Chinese in Taiwan. To investigate the reasons for this disparity, we genotyped Mycobacterium tuberculosis (MTB) strains obtained from members of different aboriginal tribes in different geographical regions of Taiwan by using molecular methods. In total, 177 isolates of MTB collected from patients at four hospitals in Taiwan from January 2006 to December 2011 were analysed by spoligotyping, mycobacterial interspersed repetitive unit-variable number tandem-repeat (MIRU-VNTR) typing. The most prevalent strains in the eastern and central regions of Taiwan were Beijing (45.7% in eastern) and Haarlem (39.1% in eastern, 37.1% in central) lineages, whereas in southern regions the most prevalent strains were EAI (47.7%) and Haarlem (20.5%) lineages. The high prevalence of EAI in southern Taiwan aborigines may be closely associated with Austronesian culture. This study provides a first overview of the M. tuberculosis strains circulating in aboriginal populations in Taiwan. The high prevalences of certain MTB lineages within aboriginal sub-populations suggest that transmission of MTB may have been restricted to close contacts.
- Published
- 2014
20. Genomics Study of
- Author
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Horng-Yunn, Dou, Yih-Yuan, Chen, Ying-Tsong, Chen, Jia-Ru, Chang, Chien-Hsing, Lin, Keh-Ming, Wu, Ming-Shian, Lin, Ih-Jen, Su, and Shih-Feng, Tsai
- Subjects
genomics study ,ethnic population ,molecular evolution ,Mycobacterium tuberculosis ,Original Research - Abstract
To better understand the transmission and evolution of Mycobacterium tuberculosis (MTB) in Taiwan, six different MTB isolates (representatives of the Beijing ancient sublineage, Beijing modern sublineage, Haarlem, East-African Indian, T1, and Latin-American Mediterranean (LAM)) were characterized and their genomes were sequenced. Discriminating among large sequence polymorphisms (LSPs) that occur once versus those that occur repeatedly in a genomic region may help to elucidate the biological roles of LSPs and to identify the useful phylogenetic relationships. In contrast to our previous LSP-based phylogeny, the sequencing data allowed us to determine actual genetic distances and to define precisely the phylogenetic relationships between the main lineages of the MTB complex. Comparative genomics analyses revealed more nonsynonymous substitutions than synonymous changes in the coding sequences. Furthermore, MTB isolate M7, a LAM-3 clinical strain isolated from a patient of Taiwanese aboriginal origin, is closely related to F11 (LAM), an epidemic tuberculosis strain isolated in the Western Cape of South Africa. The PE/PPE protein family showed a higher dn/ds ratio compared to that for all protein-coding genes. Finally, we found Haarlem-3 and LAM-3 isolates to be circulating in the aboriginal community in Taiwan, suggesting that they may have originated with post-Columbus Europeans. Taken together, our results revealed an interesting association with historical migrations of different ethnic populations, thus providing a good model to explore the global evolution and spread of MTB.
- Published
- 2016
21. Draft Genome Sequence of Mycobacterium tuberculosis Clinical Strain W06, a Prevalent Beijing Genotype Isolated in Taiwan
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Chih Hao Hsu, Yih Yuan Chen, Jia Ru Chang, Yu-Chieh Liao, Ching Yen Lin, Horng Yunn Dou, Tze Tze Liu, Hsin-Hung Lin, and Ying Chih Lo
- Subjects
Whole genome sequencing ,Genetics ,Tuberculosis ,biology ,Strain (biology) ,Bioinformatics ,biology.organism_classification ,medicine.disease ,Genome ,Mycobacterium tuberculosis ,Beijing ,Beijing genotype ,medicine ,Prokaryotes ,Molecular Biology - Abstract
Mycobacterium tuberculosis strain W06, analyzed by molecular methods, was classified as a modern Beijing M. tuberculosis strain, the most predominant strain in Taiwan. To our knowledge, this is the first draft genome announcement of a Beijing M. tuberculosis strain in Taiwan.
- Published
- 2015
22. Molecular Epidemiology of Tuberculosis in Kaohsiung City Located at Southern Taiwan, 2000-2008
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Tzong-Shi Chiueh, Jia-Ru Chang, Ih-Jen Su, Horng-Yunn Dou, Tsi-Shu Huang, Yao-Shen Chen, Fan-Chen Tseng, Jun-Ren Sun, Shu-Chen Kuo, Yih-Yuan Chen, and Wei-Chen Huang
- Subjects
Tuberculosis ,Population ,Taiwan ,lcsh:Medicine ,Drug resistance ,Polymorphism, Single Nucleotide ,Microbiology ,Mycobacterium tuberculosis ,Antibiotic resistance ,Genotype ,Drug Resistance, Bacterial ,medicine ,Humans ,education ,lcsh:Science ,Retrospective Studies ,education.field_of_study ,Molecular Epidemiology ,Multidisciplinary ,Molecular epidemiology ,biology ,business.industry ,lcsh:R ,medicine.disease ,biology.organism_classification ,Anti-Bacterial Agents ,Bacterial Typing Techniques ,Multiple drug resistance ,Streptomycin ,lcsh:Q ,business ,Genome, Bacterial ,Research Article - Abstract
BACKGROUND We present the first comprehensive analysis of Mycobacterium tuberculosis (MTB) isolates circulating in southern Taiwan. In this 9-year population-based study, the TB situation in the Kaohsiung region was characterized by genotypic analysis of 421 MTB isolates. METHODS All 421 isolates of MTB were analyzed by spoligotyping and MIRU-VNTR typing. Drug-resistance patterns were also analyzed. RESULTS The percentage of EAI (East African-Indian) strains increased across sampling years (2000-2008) in southern Taiwan, whereas the proportion of Beijing lineages remained unchanged. Clustering was more frequent with EAI genotype infections (odds ratio = 3.6, p
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- 2015
23. Draft Genome Sequences of the Mycobacterium tuberculosis Clinical Strains A2 and A4, Isolated from a Relapse Patient in Taiwan
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Horng-Yunn Dou, Yih-Yuan Chen, Tsi-Shu Huang, Hsin-Hung Lin, Jia-Ru Chang, Ih-Jen Su, and Yu-Chieh Liao
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Mycobacterium tuberculosis ,Tuberculosis ,biology ,Transfer RNA ,Genetics ,medicine ,Prokaryotes ,medicine.disease ,biology.organism_classification ,Molecular Biology ,Gene ,Genome ,Virology - Abstract
The recurrence rate of Mycobacterium tuberculosis in Taiwan is 3%. Here, we present the draft genome sequences of M. tuberculosis strains A2 and A4 from a relapse patient. The draft genome sequences comprise 4,443,031 bp and 4,487,096 bp, revealing 4,220 and 4,143 coding sequences for A2 and A4, respectively, as well as 49 tRNA genes for the both isolates.
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- 2014
24. Draft Genome Sequence of the Mycobacterium tuberculosis Clinical Isolate C2, Belonging to the Latin American–Mediterranean Family
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Yih-Yuan Chen, Horng-Yunn Dou, Yu-Chieh Liao, Jia-Ru Chang, Tsi-Shu Huang, Hsin-Hung Lin, and Ih-Jen Su
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Genetics ,Whole genome sequencing ,Latin Americans ,Tuberculosis ,biology ,biology.organism_classification ,medicine.disease ,C content ,Mycobacterium tuberculosis ,Infectious disease (medical specialty) ,Transfer RNA ,medicine ,Prokaryotes ,Molecular Biology ,Gene - Abstract
Tuberculosis remains a major infectious disease in Taiwan. Here we present the draft genome sequence of the Mycobacterium tuberculosis C2 strain, belonging to the Latin American–Mediterranean lineage. The draft genome sequence comprises 4,453,307 bp with a G+C content of 65.6%, revealing 4,390 coding genes and 45 tRNA genes.
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- 2014
25. Genomics Study ofMycobacterium tuberculosisStrains from Different Ethnic Populations in Taiwan
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Shih-Feng Tsai, Yih-Yuan Chen, Horng-Yunn Dou, Ming-Shian Lin, Ih-Jen Su, Ying-Tsong Chen, Jia-Ru Chang, Chien-Hsing Lin, and Keh-Ming Wu
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0301 basic medicine ,Comparative genomics ,Genetics ,Nonsynonymous substitution ,Phylogenetic tree ,business.industry ,030106 microbiology ,Genomics ,Biology ,biology.organism_classification ,Genome ,Computer Science Applications ,Biotechnology ,Mycobacterium tuberculosis ,03 medical and health sciences ,030104 developmental biology ,Molecular evolution ,Phylogenetics ,business ,Ecology, Evolution, Behavior and Systematics - Abstract
To better understand the transmission and evolution of Mycobacterium tuberculosis (MTB) in Taiwan, six different MTB isolates (representatives of the Beijing ancient sublineage, Beijing modern sublineage, Haarlem, East-African Indian, T1, and Latin-American Mediterranean (LAM)) were characterized and their genomes were sequenced. Discriminating among large sequence polymorphisms (LSPs) that occur once versus those that occur repeatedly in a genomic region may help to elucidate the biological roles of LSPs and to identify the useful phylogenetic relationships. In contrast to our previous LSP-based phylogeny, the sequencing data allowed us to determine actual genetic distances and to define precisely the phylogenetic relationships between the main lineages of the MTB complex. Comparative genomics analyses revealed more nonsynonymous substitutions than synonymous changes in the coding sequences. Furthermore, MTB isolate M7, a LAM-3 clinical strain isolated from a patient of Taiwanese aboriginal origin, is closely related to F11 (LAM), an epidemic tuberculosis strain isolated in the Western Cape of South Africa. The PE/PPE protein family showed a higher dn/ds ratio compared to that for all protein-coding genes. Finally, we found Haarlem-3 and LAM-3 isolates to be circulating in the aboriginal community in Taiwan, suggesting that they may have originated with post-Columbus Europeans. Taken together, our results revealed an interesting association with historical migrations of different ethnic populations, thus providing a good model to explore the global evolution and spread of MTB.
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- 2016
26. Clonal expansion of both modern and ancient genotypes of Mycobacterium tuberculosis in southern Taiwan
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Jun-Ren Sun, Wei-Feng Huang, Shu-Chen Kuo, Yih-Yuan Chen, Tzong-Shi Chiueh, Tsi-Shu Huang, Fan-Chen Tseng, Ih-Jen Su, Chien-Hsing Lin, Yao-Shen Chen, Jia-Ru Chang, and Horng-Yunn Dou
- Subjects
Bacterial Diseases ,Veterinary medicine ,Tuberculosis ,Genotype ,Epidemiology ,Southern taiwan ,Taiwan ,lcsh:Medicine ,Microbiology ,Infectious Disease Epidemiology ,Mass Spectrometry ,Mycobacterium ,Mycobacterium tuberculosis ,Beijing ,Microbial Control ,medicine ,Typing ,lcsh:Science ,Biology ,Microbial Pathogens ,Multidisciplinary ,biology ,Population Biology ,Strain (biology) ,lcsh:R ,biology.organism_classification ,medicine.disease ,Subtyping ,Emerging Infectious Diseases ,Infectious Diseases ,Medical Microbiology ,Microbial Evolution ,Medicine ,lcsh:Q ,Research Article - Abstract
We present the first comprehensive analysis of Mycobacterium tuberculosis isolates circulating in the Kaohsiung region of southern Taiwan. The major spoligotypes found in the 224 isolates studied were Beijing lineages (n = 97; 43.3%), EAI lineages (n = 72; 32.1%) and Haarlem lineages (n = 18; 8.0%). By 24 MIRU-VNTR typing, 174 patterns were identified, including 24 clusters of 74 isolates and 150 unique patterns. The combination of spoligotyping and 12-MIRU-VNTR revealed that 129 (57.6%) of the 224 isolates were clustered in 18 genotypes. Moreover, 63.6% (7/11) of infected persons younger than 30 years had a Beijing strain, which could suggest recent spread among younger persons by this family of TB strains in Kaohsiung. Among the 94 Beijing family (SIT1, SIT250 and SIT1674) isolates further analyzed for SNPs by mass spectrometry, the most frequent strain found was ST10 (n = 49; 52%), followed by ST22 (n = 17; 18%) and ST19 (n = 11; 12%). Among the EAI-Manila family isolates analyzed by region deletion-based subtyping, the most frequent strain found was RD type 1 (n = 63; 87.5%), followed by RD type 2 (n = 9; 12.5%). In our previous study, the proportion of modern Beijing strains (52.5%) in northern Taiwan was significantly higher than the proportion of EAI strains (11%). In contrast, in the present study, EAI strains comprised up to 32% of Beijing strains in southern Taiwan. In conclusion, both 'modern' (Beijing) and 'ancient' (EAI) M. tuberculosis strains are prevalent in the Kaohsiung region, perhaps suggesting that both strains are somehow more adapted to southern Taiwan. It will be interesting to investigate the dynamics of the lineage composition by different selection pressures.
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- 2012
27. Recombinant BCG coexpressing Ag85B, CFP10, and interleukin-12 induces multifunctional Th1 and memory T cells in mice
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Chih-Wei, Lin, Ih-Jen, Su, Jia-Ru, Chang, Yih-Yuan, Chen, Jang-Jih, Lu, and Horng-Yunn, Dou
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Antigens, Bacterial ,Mice, Inbred C3H ,Vaccines, Synthetic ,Base Sequence ,Th1 Cells ,Antibodies, Bacterial ,Interleukin-12 ,Mycobacterium bovis ,Mice, Inbred C57BL ,Mice ,Bacterial Proteins ,T-Lymphocyte Subsets ,BCG Vaccine ,Animals ,Cytokines ,Humans ,Tuberculosis ,Female ,Immunologic Memory ,Acyltransferases ,Spleen ,DNA Primers - Abstract
Mycobacterium tuberculosis (MTB) continues to be a leading cause of human deaths due to an infectious agent. Current efforts are focused on making better TB vaccines. We describe the generation and immunological characterization of recombinant BCG (rBCG). This rBCG was generated by incorporating an expression plasmid encoding two mycobacterial antigens (Ag85B and CFP10) and human interleukin (IL)-12 into a BCG strain. Immunogenicity studies in mice showed that rBCG coexpressing Ag85B, CFP10, and IL-12 (rBCG::Ag85B-CFP10-IL-12) induces a robust immune response in mice. The rBCG vaccine promotes a T-cell response against MTB that is characterized by a high proportion of polyfunctional and memory T cells in spleen and lung. Our results showed strong immunogenicity and mycobacterial growth inhibition of rBCG::Ag85B-CFP10 plus IL-12 than that of BCG vaccine.
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- 2011
28. Utility and evaluation of new variable-number tandem-repeat systems for genotyping mycobacterial tuberculosis isolates
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Jun-Ren Sun, Ih-Jen Su, Jia-Ru Chang, Horng-Yunn Dou, Jang-Jih Lu, and Chih-Wei Lin
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Microbiology (medical) ,Tuberculosis ,Genotype ,Minisatellite Repeats ,Biology ,Microbiology ,Polymerase Chain Reaction ,law.invention ,Mycobacterium tuberculosis ,Tandem repeat ,law ,medicine ,Humans ,Typing ,Molecular Biology ,Genotyping ,Tuberculosis, Pulmonary ,Polymerase chain reaction ,Genetics ,bacterial infections and mycoses ,medicine.disease ,biology.organism_classification ,Virology ,DNA Fingerprinting ,Bacterial Typing Techniques ,Variable number tandem repeat - Abstract
We compared mycobacterial interspersed repetitive unit (MIRU)-variable number tandem repeat (VNTR) typing to traditional spoligotyping for discriminating Mycobacterium tuberculosis (MTB) strains. Our 17-loci MIRU-VNTR typing method was found to be superior to spoligotyping for non-Beijing family strains. To extend the method we also established PCR-based rapid genotyping protocols for Beijing, East-African-Indian and U lineages.
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- 2008
29. Associations of Mycobacterium tuberculosis genotypes with different ethnic and migratory populations in Taiwan
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Wei-Chieh Miu, Ih-Jen Su, Shih-Feng Tsai, Horng-Yunn Dou, Fan-Chen Tseng, Chih-Wei Lin, Ruwen Jou, Jia-Ru Chang, and Jang-Jih Lu
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Microbiology (medical) ,Mainland China ,Tuberculosis ,Genotype ,Population ,Ethnic group ,Taiwan ,Emigrants and Immigrants ,Microbiology ,Mycobacterium tuberculosis ,Beijing ,Genetics ,medicine ,Humans ,Typing ,education ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Phylogeny ,education.field_of_study ,biology ,biology.organism_classification ,medicine.disease ,Infectious Diseases ,Demography - Abstract
The distribution of human Mycobacterium tuberculosis (MTB) genotypes is reportedly associated with geography, ethnicity and population migrations. Three groups of 208 patients with tuberculosis in Taiwan were sampled to test this observation: (1) 41 aborigines of Austronesian ethnicity, who have been inhabiting in Taiwan for more than 500 years; (2) 58 veterans of Han Chinese origin, who moved as the first generation from Mainland China to Taiwan 55-60 years ago; and (3) 109 patients representing the general Taiwanese population of Han Chinese whose ancestors migrated to Taiwan around 200-400 years ago. A total of 208 MTB isolates, one per patient, were analyzed by spoligotyping and mycobacterial interspersed repetitive unit (MIRU) typing. Beijing ancient strains and Haarlem strains predominated among aborigines, while Beijing modern strains were common among veterans and the general population. All Beijing strains were further analyzed by typing the NTF loci and RD deletion. Results suggest a chronological trend among Beijing isolates from the three groups: isolates from the aborigines had signatures compatible with ancient lineages, and those from veterans and the general population were more contemporary. Our data indicate that the distribution of MTB genotypes/strains in Taiwan is associated with different populations whose migratory activities occurred between 55 and 500 years ago. These results suggest that transmission of MTB may have been relatively restricted to close contacts.
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- 2007
30. Distinct Modes of Transmission of Tuberculosis in Aboriginal and Non-Aboriginal Populations in Taiwan
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Horng-Yunn Dou, Jun-Ren Sun, Tzong-Shi Chiueh, Jun-Jun Yeh, Jia-Ru Chang, Ih-Jen Su, Shu-Chen Kuo, Jen-Jyh Lee, Yih-Yuan Chen, and Fan-Chen Tseng
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Adult ,Male ,Tuberculosis ,Infectious Disease Control ,Adolescent ,Genotype ,Antitubercular Agents ,Taiwan ,Ethnic group ,lcsh:Medicine ,Plant Science ,Microbial Sensitivity Tests ,Minisatellite Repeats ,Disease Surveillance ,Mycobacterium tuberculosis ,Asian People ,Drug Resistance, Multiple, Bacterial ,Medicine and Health Sciences ,Ethnicity ,Humans ,Medicine ,lcsh:Science ,Tuberculosis, Pulmonary ,Aged ,Multidisciplinary ,biology ,business.industry ,Multi-drug-resistant tuberculosis ,lcsh:R ,Biology and Life Sciences ,Extensively drug-resistant tuberculosis ,Odds ratio ,Plant Pathology ,Middle Aged ,biology.organism_classification ,medicine.disease ,Multiple drug resistance ,Infectious Diseases ,Infectious Disease Surveillance ,lcsh:Q ,Female ,business ,Genome, Bacterial ,Research Article ,Multilocus Sequence Typing ,Demography - Abstract
Tuberculosis incidence among aborigines is significantly higher than for Han Chinese in Taiwan, but the extent to which Mycobacterium tuberculosis (MTB) strain characteristics contribute to this difference is not well understood. MTB isolates from aborigines and Han Chinese living in eastern and southern Taiwan, the major regions of aborigines, were analyzed by spoligotyping and 24-loci MIRU-VNTR. In eastern Taiwan, 60% of aboriginal patients were ≤20 years old, significantly younger than the non-aboriginal patients there; aborigines were more likely to have clustered MTB isolates than Han Chinese (odds ratio (OR) = 5.98, p
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- 2014
31. Genetic Diversity of the Mycobacterium tuberculosis Beijing Family Based on SNP and VNTR Typing Profiles in Asian Countries
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Jia-Ru Chang, Ih-Jen Su, Jun-Ren Sun, Tsi-Shu Huang, Yih-Yuan Chen, Shu-Chen Kuo, Wei-Feng Huang, Horng-Yunn Dou, Tzong-Shi Chiueh, and Yao-Shen Chen
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Bacterial Diseases ,DNA, Bacterial ,Genotype ,Taiwan ,lcsh:Medicine ,Minisatellite Repeats ,Biology ,Microbiology ,Polymerase Chain Reaction ,Polymorphism, Single Nucleotide ,Mycobacterium ,Japan ,Beijing ,Tandem repeat ,Republic of Korea ,Genetic variation ,Genetics ,Tuberculosis ,Humans ,Evolutionary Systematics ,Typing ,lcsh:Science ,Genotyping ,Alleles ,Phylogeny ,Evolutionary Biology ,Genetic diversity ,Multidisciplinary ,Phylogenetic tree ,Multi-Drug-Resistant Tuberculosis ,lcsh:R ,Genetic Variation ,Mycobacterium tuberculosis ,Thailand ,bacterial infections and mycoses ,Bacterial Pathogens ,Bacterial Typing Techniques ,Phylogenetics ,Phylogeography ,Variable number tandem repeat ,Infectious Diseases ,Genetic Loci ,Genetics of Disease ,Microbial Evolution ,Medicine ,lcsh:Q ,Research Article - 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.
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- 2012
32. Molecular epidemiology and evolutionary genetics of Mycobacterium tuberculosisin Taipei
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Jun-Ren Sun, Shi-Yi Lee, Chih-Wei Lin, Horng-Yunn Dou, Ih-Jen Su, Fan-Chen Tseng, Jia-Ru Chang, Wen-Shing Tsai, and Jang-Jih Lu
- Subjects
DNA, Bacterial ,Male ,Tuberculosis ,Taiwan ,Minisatellite Repeats ,Drug resistance ,lcsh:Infectious and parasitic diseases ,Evolution, Molecular ,Mycobacterium tuberculosis ,Beijing ,Drug Resistance, Bacterial ,Genotype ,medicine ,Humans ,lcsh:RC109-216 ,Typing ,Tuberculosis, Pulmonary ,Molecular Epidemiology ,Molecular epidemiology ,biology ,biology.organism_classification ,medicine.disease ,Virology ,Bacterial Typing Techniques ,Infectious Diseases ,Parasitology ,Female ,Reagent Kits, Diagnostic ,Research Article - Abstract
Background The control of tuberculosis in densely populated cities is complicated by close human-to-human contacts and potential transmission of pathogens from multiple sources. We conducted a molecular epidemiologic analysis of 356 Mycobacterium tuberculosis (MTB) isolates from patients presenting pulmonary tuberculosis in metropolitan Taipei. Classical antibiogram studies and genetic characterization, using mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing and spoligotyping, were applied after culture. Methods A total of 356 isolates were genotyped by standard spoligotyping and the strains were compared with in the international spoligotyping database (SpolDB4). All isolates were also categorized using the 15 loci MIRU-VNTR typing method and combin with NTF locus and RD deletion analyses. Results Of 356 isolates spoligotyped, 290 (81.4%) displayed known spoligotypes and 66 were not identified in the database. Major spoligotypes found were Beijing lineages (52.5%), followed by Haarlem lineages (13.5%) and EAI plus EAI-like lineages (11%). When MIRU-VNTR was employed, 140 patterns were identified, including 36 clusters by 252 isolates and 104 unique patterns, and the largest cluster comprised 95 isolates from the Beijing family. The combination of spoligotyping and MIRU-VNTR revealed that 236 (67%) of the 356 isolates were clustered in 43 genotypes. Strains of the Beijing family was more likely to be of modern strain and a higher percentage of multiple drug resistance than other families combined (P = 0.08). Patients infected with Beijing strains were younger than those with other strains (mean 58.7 vs. 64.2, p = 0.02). Moreover, 85.3% of infected persons younger than 25 years had Beijing modern strain, suggesting a possible recent spread in the young population by this family of TB strain in Taipei. Conclusion Our data on MTB genotype in Taipei suggest that MTB infection has not been optimally controlled. Control efforts should be reinforced in view of the high prevalence of the Beijing strain in young population and association with drug resistance.
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