Deletion of RD1 from Mycobacterium tuberculosis mimics bacille Calmette-Guérin attenuation

J Infect Dis. 2003 Jan 1;187(1):117-23. doi: 10.1086/345862. Epub 2002 Dec 2.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • BCG Vaccine*
  • Cells, Cultured
  • Gene Deletion*
  • Genes, Bacterial / physiology*
  • Humans
  • Macrophages / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mycobacterium tuberculosis / genetics*
  • Mycobacterium tuberculosis / pathogenicity*
  • Tuberculosis, Pulmonary / pathology
  • Vaccines, Attenuated


  • BCG Vaccine
  • Vaccines, Attenuated