Deletion of RD1 from Mycobacterium tuberculosis Mimics Bacille Calmette‐Guérin Attenuation
Open accessAbstract
The tuberculosis (TB) vaccine bacille Calmette-Guérin (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.
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M. tuberculosis and M. marinum mutants with deletion of ESX-1 are attenuated in their respective hosts.
“M. tuberculosis and M. marinum mutants with deletion of ESX-1 are attenuated in their respective hosts (61)(62)(63)(64), which is in line with the attenuation of”
From ESX/Type VII Secretion Systems—An Important Way Out for Mycobacterial Proteins (2019) · cites this paper as [61]
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Self-citation
- Authors
- Lewis, K. N., Liao, R., Guinn, K. M., Hickey, M. J., Smith, S., Behr, M. A., & Sherman, D. R.
- Affiliations
- University of Washington (US)
- Pediatrics and Genetics (US)
- McGill University (CA)
- Venue
- The Journal of Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-01
- Volume
- 187
- Issue
- 1
- Pages
- 117-123
- ISSN
- 0022-1899 (ISSN-L)
- 1537-6613
- PMC
- PMC1458498
- OpenAlex
- W2106942635
- Cited by
- 588
- References
- 39
- Citations by year
- 2026: 16 · 2025: 23 · 2024: 16 · 2023: 16 · 2022: 18 · 2021: 24 · 2020: 31 · 2019: 25 · 2018: 15 · 2017: 22 · 2016: 31 · 2015: 29 · 2014: 35 · 2013: 34 · 2012: 24
- FWCI
- 15.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Infectious Diseases (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL64550, R01HL068533, R01HL064550, HL68533)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Health Sciences › Medicine › Surgery › Infectious Diseases and Tuberculosis
- Health Sciences › Medicine › Epidemiology › Mycobacterium research and diagnosis
- Keywords
- Mycobacterium tuberculosis, virulence, Mycobacterium tuberculosis H37Rv, deletion mutants, ESAT-6, CFP-10, macrophage infection, mouse model, tuberculosis vaccine
- MeSH terms
- Animals, BCG Vaccine, Cells, Cultured, Genes, Bacterial, Humans, Macrophages, Mice, Inbred C57BL, Mycobacterium tuberculosis, Tuberculosis, Pulmonary, Vaccines, Attenuated, Gene Deletion, Mice
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