000151248 001__ 151248
000151248 005__ 20181203021958.0
000151248 022__ $$a0950-382X
000151248 02470 $$2PMID$$a12410828
000151248 0247_ $$2doi$$a10.1046/j.1365-2958.2002.03237.x
000151248 037__ $$aARTICLE
000151248 245__ $$aLoss of RD1 contributed to the attenuation of the live tuberculosis vaccines Mycobacterium bovis BCG and Mycobacterium microti
000151248 269__ $$a2002
000151248 260__ $$c2002
000151248 336__ $$aJournal Articles
000151248 520__ $$aAlthough large human populations have been safely immunized against tuberculosis with two live vaccines, Mycobacterium bovis BCG or Mycobacterium microti, the vole bacillus, the molecular basis for the avirulence of these vaccine strains remains unknown. Comparative genomics has identified a series of chromosomal deletions common to both virulent and avirulent species but only a single locus, RD1, that has been deleted from M. bovis BCG and M. microti. Restoration of RD1, by gene knock-in, resulted in a marked change in colonial morphology towards that of virulent tubercle bacilli. Three RD1-encoded proteins were localized in the cell wall, and two of them, the immunodominant T-cell antigens ESAT-6 and CFP-10, were also found in culture supernatants. The BCG::RD1 and M. microti::RD1 knock-ins grew more vigorously than controls in immunodeficient mice, inducing extensive splenomegaly and granuloma formation. Increased persistence and partial reversal of attenuation were observed when immunocompetent mice were infected with the BCG::RD1 knock-in, whereas BCG controls were cleared. Knocking-in five other RD loci did not affect the virulence of BCG. This study describes a genetic lesion that contributes to safety and opens new avenues for vaccine development.
000151248 6531_ $$aGene Deletion
000151248 700__ $$aPym, Alexander S
000151248 700__ $$aBrodin, Priscille
000151248 700__ $$aBrosch, Roland
000151248 700__ $$aHuerre, Michel
000151248 700__ $$g177247$$aCole, Stewart T$$0243892
000151248 773__ $$j46$$tMolecular microbiology$$k3$$q709-17
000151248 909C0 $$xU11742$$0252302$$pUPCOL
000151248 909CO $$pSV$$particle$$ooai:infoscience.tind.io:151248
000151248 937__ $$aEPFL-ARTICLE-151248
000151248 973__ $$rREVIEWED$$sPUBLISHED$$aOTHER
000151248 980__ $$aARTICLE