In vivo characteristics of Korean Beijing Mycobacterium tuberculosis strain K1 in an aerosol challenge model and in the Cornell latent tuberculosis model

Jeon, Bo Young; Kwak, Jeong-Yeon; Hahn, Mi Young; Eum, Seok Yong; Yang, Ji-Yeon; Kim, Seung Cheol; Cho, Sang Nae

doi:10.1099/jmm.0.047027-0

Cited by 22 publications

(27 citation statements)

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“…The Mtb K strain phylogenetically belongs to the Beijing genotype; it was most widely isolated in an outbreak of pulmonary TB in senior high schools in South Korea [ 21 ]. Importantly, our previous study showed that Mtb K replicated rapidly during the early stages of infection in a murine model of TB with a more severe pathology [ 22 ]. During the study, intriguingly, we observed that there was only a small colony forming unit (CFU) difference at later time points (> 12 weeks post-infection) between the K strain and H37Rv, but the K strain led to death earlier than H37Rv because of an excessive host immune response [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Virulence-Dependent Alterations in the Kinetics of Immune Cells during Pulmonary Infection by Mycobacterium tuberculosis

Kim

Bin

et al. 2015

PLoS ONE

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A better understanding of the kinetics of accumulated immune cells that are involved in pathophysiology during Mycobacterium tuberculosis (Mtb) infection may help to facilitate the development of vaccines and immunological interventions. However, the kinetics of innate and adaptive cells that are associated with pathogenesis during Mtb infection and their relationship to Mtb virulence are not clearly understood. In this study, we used a mouse model to compare the bacterial burden, inflammation and kinetics of immune cells during aerogenic infection in the lung between laboratory-adapted strains (Mtb H37Rv and H37Ra) and Mtb K strain, a hyper-virulent W-Beijing lineage strain. The Mtb K strain multiplied more than 10- and 3.54-fold more rapidly than H37Ra and H37Rv, respectively, during the early stage of infection (at 28 days post-infection) and resulted in exacerbated lung pathology at 56 to 112 days post-infection. Similar numbers of innate immune cells had infiltrated, regardless of the strain, by 14 days post-infection. High, time-dependent frequencies of F4/80-CD11c+CD11b-Siglec-H+PDCA-1+ plasmacytoid DCs and CD11c-CD11b+Gr-1int cells were observed in the lungs of mice that were infected with the Mtb K strain. Regarding adaptive immunity, Th1 and Th17 T cells that express T-bet and RORγt, respectively, significantly increased in the lungs that were infected with the laboratory-adapted strains, and the population of CD4+CD25+Foxp3+ regulatory T cells was remarkably increased at 112 days post-infection in the lungs of mice that were infected with the K strain. Collectively, our findings indicate that the highly virulent Mtb K strain may trigger the accumulation of pDCs and Gr1intCD11b+ cells with the concomitant down-regulation of the Th1 response and the maintenance of an up-regulated Th2 response without inducing a Th17 response during chronic infection. These results will help to determine which immune system components must be considered for the development of tuberculosis (TB) vaccines and immunological interventions.

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Section: Introductionmentioning

confidence: 99%

Virulence-Dependent Alterations in the Kinetics of Immune Cells during Pulmonary Infection by Mycobacterium tuberculosis

Kim

Bin

et al. 2015

PLoS ONE

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“…Beijing/K strains were identified as the major cause of pulmonary TB outbreaks (14) and were associated with drug resistance (13) in South Korea. The Beijing/K strain has rapid replication with more severe pathologies at early times after infection compared to M. tuberculosis H37Rv in mice (15,16).…”

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confidence: 99%

Protective Vaccine Efficacy of the Complete Form of PPE39 Protein from Mycobacterium tuberculosis Beijing/K Strain in Mice

Kim

Hur

et al. 2017

Clin Vaccine Immunol

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The aim of this study was to evaluate the protective efficacy of MTBK_ 24820, a complete form of PPE39 protein derived from a predominant Beijing/K strain of Mycobacterium tuberculosis in South Korea. Mice were immunized with MTKB_24820, M. bovis Bacilli Calmette-Guérin (BCG), or adjuvant prior to a high-dosed Beijing/K strain aerosol infection. After 4 and 9 weeks, bacterial loads were determined and histopathologic and immunologic features in the lungs and spleens of the M. tuberculosis-infected mice were analyzed. Putative immunogenic T-cell epitopes were examined using synthetic overlapping peptides. Successful immunization of MTBK_24820 in mice was confirmed by increased IgG responses (P Ͻ 0.05) and recalled gamma interferon (IFN-␥), interleukin-2 (IL-2), IL-6, and IL-17 responses (P Ͻ 0.05 or P Ͻ 0.01) to MTBK_24820. After challenge with the Beijing/K strain, an approximately 0.5 to 1.0 log 10 reduction in CFU in lungs and fewer lung inflammation lesions were observed in MTBK_24820-immunized mice compared to those for control mice. Moreover, MTBK_24820 immunization elicited significantly higher numbers of CD4 ϩ T cells producing protective cytokines, such as IFN-␥ and IL-17, in lungs and spleens (P Ͻ 0.01) and CD4 ϩ multifunctional T cells producing IFN-␥, tumor necrosis factor alpha (TNF-␣), and/or IL-17 (P Ͻ 0.01) than in control mice, suggesting protection comparable to that of BCG against the hypervirulent Beijing/K strain. The dominant immunogenic T-cell epitopes that induced IFN-␥ production were at the N terminus (amino acids 85 to 102 and 217 to 234). Its vaccine potential, along with protective immune responses in vivo, may be informative for vaccine development, particularly in regions where the M. tuberculosis Beijing/K-strain is frequently isolated from TB patients.

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“…M. tuberculosis K replicates rapidly during the early stages of infection in a murine model of TB, causing a more severe pathology and a high level of reactivation from latent infection [ 14 ]. In addition, the Bacillus-Calmette-Guérin vaccination is less effective against an M. tuberculosis K infection than H37Rv T (unpublished data).…”

Section: Introductionmentioning

confidence: 99%

Complete genome sequence of Mycobacterium tuberculosis K from a Korean high school outbreak, belonging to the Beijing family

Han¹,

Song²,

Cho³

et al. 2015

Stand in Genomic Sci

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Mycobacterium tuberculosis K, a member of the Beijing family, was first identified in 1999 as the most prevalent genotype in South Korea among clinical isolates of M. tuberculosis from high school outbreaks. M. tuberculosis K is an aerobic, non-motile, Gram-positive, and non-spore-forming rod-shaped bacillus. A transmission electron microscopy analysis displayed an abundance of lipid bodies in the cytosol. The genome of the M. tuberculosis K strain was sequenced using two independent sequencing methods (Sanger and Illumina). Here, we present the genomic features of the 4,385,518-bp-long complete genome sequence of M. tuberculosis K (one chromosome, no plasmid, and 65.59 % G + C content) and its annotation, which consists of 4194 genes (3447 genes with predicted functions), 48 RNA genes (3 rRNA and 45 tRNA) and 261 genes with peptide signals.Electronic supplementary materialThe online version of this article (doi:10.1186/s40793-015-0071-4) contains supplementary material, which is available to authorized users.

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In vivo characteristics of Korean Beijing Mycobacterium tuberculosis strain K1 in an aerosol challenge model and in the Cornell latent tuberculosis model

Cited by 22 publications

References 20 publications

Virulence-Dependent Alterations in the Kinetics of Immune Cells during Pulmonary Infection by Mycobacterium tuberculosis

Virulence-Dependent Alterations in the Kinetics of Immune Cells during Pulmonary Infection by Mycobacterium tuberculosis

Protective Vaccine Efficacy of the Complete Form of PPE39 Protein from Mycobacterium tuberculosis Beijing/K Strain in Mice

Complete genome sequence of Mycobacterium tuberculosis K from a Korean high school outbreak, belonging to the Beijing family

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