Mapping the phylogenyand lineage history of geographically distinct BCG vaccine strains
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PROVIDER: PRJEB60755 | ENA |
REPOSITORIES: ENA
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Project description:Mapping the phylogeny and lineage history of geographically distinct BCG vaccine strains
| PRJEB61685 | ENA
Project description:Mapping the phylogeny and lineage history of geographically distinct BCG vaccine strains
| PRJEB55451 | ENA
Project description:Genetically distinct lineages of Mycobacterium tuberculosis differ in their virulence, transmissibility, and immune evasion capacity. The modern Lineage 2-Beijing (L2-B) clade of Mtb, which is highly prevalent in Asia and now globally distributed, is associated with resistance to the bacille Calmette Guerin (BCG) vaccine. Using a murine BCG vaccination model followed by aerosol challenge with geographically matched L2-B or Lineage 4 clinical isolates, we examined how L2-B circumvents vaccine-induced immunity. BCG-trained alveolar macrophages showed impaired control of L2-B growth in vitro. Spatial transcriptomic profiling of infected lungs revealed broad transcriptional reprogramming, including selective suppression of pathways essential for macrophage activation and trained innate immunity. Similar immune dysregulation was observed in peripheral blood from BCG-vaccinated household contacts of L2-B smear-positive TB patients. Together, these findings define mechanisms by which L2-B evades immune control, highlight key components of BCG-induced protection, and support re-evaluation of current TB vaccine strategies.
2026-04-26 | GSE328649 | GEO
Project description: Not available
| S-EPMC10483423 | biostudies-literature
Project description:Mycobacterium tuberculosis is the causative agent of tuberculosis, a disease that affects one-third of the world’s population. The sole extant vaccine for tuberculosis is the live attenuated Mycobacterium bovis bacille Calmette-Guerin (BCG). We examined 13 representative BCG strains from around the world to ascertain their ability to express DosR-regulated dormancy antigens. These are known to be recognized by T-cells of M. tuberculosis infected individuals, especially those harboring latent infections. Differences in expression of these antigens could be valuable for use as diagnostic markers to distinguish BCG vaccination from latent tuberculosis. We determined that all BCG strains were defective for induction of two dormancy genes, narK2 (Rv1737c) and narX (Rv1736c). NarK2 is known to be necessary for nitrate respiration during anaerobic dormancy. Analysis of the narK2/X promoter region revealed a base substitution mutation in all tested BCG strains and M. bovis in comparison to the M. tuberculosis sequence. We also show that nitrate reduction by BCG strains during dormancy was greatly reduced compared to M. tuberculosis and varied between tested strains. Several dormancy regulon transcriptional differences were also identified among the strains, as well as variation in their growth and survival. These findings demonstrate defects in DosR regulon expression during dormancy and phenotypic variation between commonly used BCG vaccine strains. 12 different BCG strains were examined as well as M. tuberculosis H37Rv and M. bovis. Two arrays per strain were analyzed, one with the addition of nitric oxide and the other utilizing hypoxia treatment, both conditions shown to induce expression of the dormancy regulon. The reference sample for each array was log phase M. tuberculosis H37Rv.
2008-05-03 | E-GEOD-11315 | biostudies-arrayexpress
Project description:The current tuberculosis vaccine, Bacillus Calmette-Guérin (BCG), provides insufficient protection. We deleted the NADH dehydrogenase 1 subunit G (nuoG) gene from BCG ΔureC::hly, the most advanced live vaccine candidate in clinical development. Removal of nuoG enhanced co-localisation of LC3 to bacteria in human host cells. BCG ΔureC::hly ΔnuoG vaccination was safer than BCG and improved efficacy of BCG ΔureC::hly by reducing tuberculosis load in murine lungs 1000-fold.
2016-05-03 | GSE74282 | GEO
Project description:Mycobacterium tuberculosis is the causative agent of tuberculosis, a disease that affects one-third of the world’s population. The sole extant vaccine for tuberculosis is the live attenuated Mycobacterium bovis bacille Calmette-Guerin (BCG). We examined 13 representative BCG strains from around the world to ascertain their ability to express DosR-regulated dormancy antigens. These are known to be recognized by T-cells of M. tuberculosis infected individuals, especially those harboring latent infections. Differences in expression of these antigens could be valuable for use as diagnostic markers to distinguish BCG vaccination from latent tuberculosis. We determined that all BCG strains were defective for induction of two dormancy genes, narK2 (Rv1737c) and narX (Rv1736c). NarK2 is known to be necessary for nitrate respiration during anaerobic dormancy. Analysis of the narK2/X promoter region revealed a base substitution mutation in all tested BCG strains and M. bovis in comparison to the M. tuberculosis sequence. We also show that nitrate reduction by BCG strains during dormancy was greatly reduced compared to M. tuberculosis and varied between tested strains. Several dormancy regulon transcriptional differences were also identified among the strains, as well as variation in their growth and survival. These findings demonstrate defects in DosR regulon expression during dormancy and phenotypic variation between commonly used BCG vaccine strains. Keywords: Comparison of induction of a subset of genes between various mycobacterial strains.
2008-05-03 | GSE11315 | GEO
Project description:Investigation of the Types and Expression Levels of Target Proteins Regulated by the Transcription Factor NapR Following Its Overexpression in Intracellular BCG vaccine
2025-02-28 | PXD059682 | Pride
Project description:The BCG vaccine (Bacille Calmette-Guerin), only prophylactic measure against tuberculosis (TB), was obtained in the early twentieth century by Calmette and Guérin after 231 passages of a M. bovis clinical isolate in medium containing glycerin and bovine bile. Its protective efficacy against pulmonary TB in adults varies from 0-80% and the genetic differences among vaccines strains used worldwide contribute to this variation. The Brazilian vaccine strain, BCG Moreau, is considered a primitive strain and more immunogenic, closer to the original BCG when compared to newer strains, such as BCG Pasteur (reference strain). The characterization of BCG sub-strains can contribute not only to a better understanding of the vaccine and its protective effect, but also, in elucidating how different BCG culture conditions may contribute to the impact on the host's immune response. Thus, we aimed to characterize the differences in gene expression through the intracellular proteomic profile of BCG Moreau and Pasteur strains, cultivated in Sauton or 7H9 medium, using the methodology of two-dimensional electrophoresis (2DE) and mass spectrometry.
2025-10-23 | PXD030179 | Pride
Project description:proteomes of host cells infected with BCG during the early stage at 12, 24, and 48 h respectively to identify the potential bacterial components derived from BCG.
| PXD076732 |