ArticleInfection and immunity2011
Region of difference 2 contributes to virulence of Mycobacterium tuberculosis.
Article in Infection and immunity, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
17 citing papers in PubMed, 43 citations in OpenAlex.
- Phenotypic and genotypic features of the Mycobacterium tuberculosis lineage 1 subgroup in central Vietnam.Scientific reports · 2021Trial
- Review
- Mapping the phylogeny and lineage history of geographically distinct BCG vaccine strains.Microbial genomics · 2023Article
- Effects ofAnnals of translational medicine · 2022Article
- Insights into the ancestry evolution of theNAR genomics and bioinformatics · 2021Article
- Shared Pathogenomic Patterns Characterize a New Phylotype, Revealing Transition toward Host-Adaptation Long before Speciation of Mycobacterium tuberculosis.Genome biology and evolution · 2019Article
- Screening Mycobacterium tuberculosis Secreted Proteins Identifies Mpt64 as a Eukaryotic Membrane-Binding Bacterial Effector.mSphere · 2019Article
- Loss of Lipid Virulence Factors Reduces the Efficacy of the BCG Vaccine.Scientific reports · 2016Article
- Genomic expression catalogue of a global collection of BCG vaccine strains show evidence for highly diverged metabolic and cell-wall adaptations.Scientific reports · 2015Article
- Identification of novel mutations associated with clofazimine resistance in Mycobacterium tuberculosis.The Journal of antimicrobial chemotherapy · 2015Article
- Mycobacterium tuberculosis strains of the modern sublineage of the Beijing family are more likely to display increased virulence than strains of the ancient sublineage.Journal of clinical microbiology · 2014Article
- Novel GMO-Based Vaccines against Tuberculosis: State of the Art and Biosafety Considerations.Vaccines · 2014Review
- Virulence factors of the Mycobacterium tuberculosis complex.Virulence · 2013Review
- Systems-based approaches to probing metabolic variation within the Mycobacterium tuberculosis complex.PloS one · 2013Article
- Different transcriptional profiles of RAW264.7 infected with Mycobacterium tuberculosis H37Rv and BCG identified via deep sequencing.PloS one · 2012Article
- A DNA vaccine expressing CFP21 and MPT64 fusion protein enhances BCG-induced protective immunity against Mycobacterium tuberculosis infection in mice.Medical microbiology and immunology · 2011Article
- Assessing and screening for T-cell epitopes from Mycobacterium tuberculosis RD2 proteins for the diagnosis of active tuberculosis.The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious DiseasesArticle
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Mycobacterium bovis BCG strains are live, attenuated vaccines generated through decades of in vitro passage. Because in vitro growth does not select for interaction with the host, it has been hypothesized that genetic loci lost from BCG code for virulence determinants that are dispensable for growth in the laboratory, as exemplified by Region of Difference 1 (RD1), which was lost during the original derivation of BCG between 1908 and 1921. Region of Difference 2 (RD2) was lost during the ongoing propagation of BCG between 1927 and 1931, a time that coincides with reports of the ongoing attenuation of the vaccine. In this study, RD2 has been disrupted in M. tuberculosis H37Rv to test whether its loss contributed to the further attenuation of BCG. The deletion of RD2 did not affect in vitro growth; in contrast, the mutant manifested a decrease in pulmonary and splenic bacterial burdens and reduced pathology in C57BL/6 mice at early time points. This attenuated phenotype was complemented by reintroducing the genes Rv1979c to Rv1982 (including mpt64) but not Rv1985c to Rv1986. In RAW 264.7 macrophages, H37Rv:ΔRD2 showed a decreased proliferation and impaired modulation of the host innate immune response; both observations were complemented with Rv1979c to Rv1982. To test the effect of RD2 disruption on innate immunity, Rag(-/-) mice were infected; H37Rv:ΔRD2 had increased survival times compared those of H37Rv. These findings support the notion that the safety profile of certain BCG vaccines stems from multiple attenuating mutations, with the RD2 deletion resulting in a less-virulent organism through the impaired bacterial manipulation of the host innate immune response.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.