Mycobacterium tuberculosis H37Rv: Delta RD1 is more virulent than M. bovis bacille Calmette-Guérin in long-term murine infection.
Region of difference (RD1) genes are present in virulent Mycobacterium tuberculosis but not the vaccine strain M. bovis bacille Calmette-Guérin (BCG). The deletion of RD1 from M. tuberculosis produces an attenuation strikingly like that of BCG, which suggests the use of RD1 mutant strains for improvement of the tuberculosis (TB) vaccine. We performed long-term murine infection with M. tuberculosis H37Rv: Delta RD1 and BCG. Mice infected with H37Rv: Delta RD1 gained less weight than did BCG-infected control mice, and, after >1 year, their lungs harbored many more bacteria and displayed significant levels of inflammation. This difference in virulence has important implications for the pursuit of strains lacking RD1 in the development of the TB vaccine.
Sherman
David R
DR
Department of Pathobiology, University of Washington, Seattle 98195-7238, USA. dsherman@u.washington.edu
Guinn
Kristi M
KM
Hickey
Mark J
MJ
Mathur
Sanjeev K
SK
Zakel
Kelly L
KL
Smith
Sherilyn
S
D000818:Animals; D001500:BCG Vaccine; D017353:Gene Deletion; D005798:Genes, Bacterial; D006801:Humans; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000472:pathogenicity*; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000472:pathogenicity*; D032581:Tuberculosis Vaccines; D014397:Tuberculosis, Pulmonary / Q000382:microbiology / Q000473:pathology*; D014613:Vaccines, Attenuated; D014774:Virulence
D001500:BCG Vaccine; D032581:Tuberculosis Vaccines; D014613:Vaccines, Attenuated