Deletion of RD1 from Mycobacterium tuberculosis mimics bacille Calmette-Guérin attenuation
Autor: | Kaeryn N. Lewis, Mark J. Hickey, David R. Sherman, Marcel A. Behr, Sherilyn Smith, Kristi M. Guinn, Reiling Liao |
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Rok vydání: | 2002 |
Předmět: |
Tuberculosis
Virulence medicine.disease_cause Vaccines Attenuated complex mixtures Article Microbiology Mycobacterium tuberculosis Mice Antigen medicine Immunology and Allergy Animals Humans Tuberculosis Pulmonary Cells Cultured Mutation CFP-10 biology Macrophages medicine.disease biology.organism_classification bacterial infections and mycoses Virology Mice Inbred C57BL Infectious Diseases Genes Bacterial ESAT-6 BCG Vaccine BCG vaccine Gene Deletion |
Zdroj: | The Journal of infectious diseases. 187(1) |
ISSN: | 0022-1899 |
Popis: | The tuberculosis (TB) vaccine bacille Calmette-Guerin (BCG) is a live attenuated organism, but the mutation responsible for its attenuation has never been defined. Recent genetic studies identified a single DNA region of difference, RD1, which is absent in all BCG strains and present in all Mycobacterium tuberculosis (MTB) strains. The 9 open-reading frames predicted within this 9.5-kb region are of unknown function, although they include the TB-specific immunodominant antigens ESAT-6 and CFP-10. In this study, RD1 was deleted from MTB strain H37Rv, and virulence of H37Rv:DeltaRD1 was assessed after infections of the human macrophage-like cell line THP-1, human peripheral blood monocyte-derived macrophages, and C57BL/6 mice. In each of these systems, the H37Rv:DeltaRD1 strain was strikingly less virulent than MTB and was very similar to BCG controls. Therefore, it was concluded that genes within or controlled by RD1 are essential for MTB virulence and that loss of RD1 was important in BCG attenuation. |
Databáze: | OpenAIRE |
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