Hewinson RG

References (2)

Title : Genome plasticity of BCG and impact on vaccine efficacy - Brosch_2007_Proc.Natl.Acad.Sci.U.S.A_104_5596
Author(s) : Brosch R , Gordon SV , Garnier T , Eiglmeier K , Frigui W , Valenti P , Dos Santos S , Duthoy S , Lacroix C , Garcia-Pelayo C , Inwald JK , Golby P , Garcia JN , Hewinson RG , Behr MA , Quail MA , Churcher C , Barrell BG , Parkhill J , Cole ST
Ref : Proc Natl Acad Sci U S A , 104 :5596 , 2007
Abstract : To understand the evolution, attenuation, and variable protective efficacy of bacillus Calmette-Guerin (BCG) vaccines, Mycobacterium bovis BCG Pasteur 1173P2 has been subjected to comparative genome and transcriptome analysis. The 4,374,522-bp genome contains 3,954 protein-coding genes, 58 of which are present in two copies as a result of two independent tandem duplications, DU1 and DU2. DU1 is restricted to BCG Pasteur, although four forms of DU2 exist; DU2-I is confined to early BCG vaccines, like BCG Japan, whereas DU2-III and DU2-IV occur in the late vaccines. The glycerol-3-phosphate dehydrogenase gene, glpD2, is one of only three genes common to all four DU2 variants, implying that BCG requires higher levels of this enzyme to grow on glycerol. Further amplification of the DU2 region is ongoing, even within vaccine preparations used to immunize humans. An evolutionary scheme for BCG vaccines was established by analyzing DU2 and other markers. Lesions in genes encoding sigma-factors and pleiotropic transcriptional regulators, like PhoR and Crp, were also uncovered in various BCG strains; together with gene amplification, these affect gene expression levels, immunogenicity, and, possibly, protection against tuberculosis. Furthermore, the combined findings suggest that early BCG vaccines may even be superior to the later ones that are more widely used.
ESTHER : Brosch_2007_Proc.Natl.Acad.Sci.U.S.A_104_5596
PubMedSearch : Brosch_2007_Proc.Natl.Acad.Sci.U.S.A_104_5596
PubMedID: 17372194
Gene_locus related to this paper: myctu-a85a , myctu-a85b , myctu-a85c , myctu-bpoC , myctu-cut3 , myctu-cutas2 , myctu-d5yk66 , myctu-ephB , myctu-ephc , myctu-ephd , myctu-ephE , myctu-hpx , myctu-linb , myctu-lipG , myctu-lipJ , myctu-LIPS , myctu-lipv , myctu-LPQC , myctu-LPQP , myctu-MBTB , myctu-metx , myctu-mpt51 , myctu-MT1628 , myctu-p71654 , myctu-p95011 , myctu-PKS6 , myctu-PKS13 , myctu-ppe42 , myctu-ppe63 , myctu-Rv1430 , myctu-RV0045C , myctu-Rv0077c , myctu-Rv0151c , myctu-Rv0152c , myctu-Rv0159c , myctu-Rv0160c , myctu-rv0183 , myctu-Rv0217c , myctu-Rv0220 , myctu-Rv0272c , myctu-RV0293C , myctu-RV0457C , myctu-RV0519C , myctu-RV0774C , myctu-RV0782 , myctu-RV0840C , myctu-Rv1069c , myctu-Rv1076 , myctu-RV1123C , myctu-Rv1184c , myctu-Rv1191 , myctu-RV1192 , myctu-RV1215C , myctu-Rv1399c , myctu-Rv1400c , myctu-Rv1426c , myctu-RV1639C , myctu-RV1683 , myctu-RV1758 , myctu-Rv1800 , myctu-Rv1833c , myctu-Rv2045c , myctu-RV2054 , myctu-Rv2284 , myctu-RV2296 , myctu-Rv2385 , myctu-Rv2485c , myctu-RV2627C , myctu-RV2672 , myctu-RV2695 , myctu-RV2765 , myctu-RV2800 , myctu-RV2854 , myctu-Rv2970c , myctu-Rv3084 , myctu-Rv3097c , myctu-rv3177 , myctu-Rv3312c , myctu-RV3452 , myctu-RV3473C , myctu-Rv3487c , myctu-Rv3569c , myctu-Rv3591c , myctu-RV3724 , myctu-Rv3802c , myctu-Rv3822 , myctu-y0571 , myctu-y963 , myctu-Y1834 , myctu-y1835 , myctu-y2079 , myctu-yc88 , myctu-ym23 , myctu-ym24 , myctu-YR15 , myctu-yt28

Title : The complete genome sequence of Mycobacterium bovis - Garnier_2003_Proc.Natl.Acad.Sci.U.S.A_100_7877
Author(s) : Garnier T , Eiglmeier K , Camus JC , Medina N , Mansoor H , Pryor M , Duthoy S , Grondin S , Lacroix C , Monsempe C , Simon S , Harris B , Atkin R , Doggett J , Mayes R , Keating L , Wheeler PR , Parkhill J , Barrell BG , Cole ST , Gordon SV , Hewinson RG
Ref : Proc Natl Acad Sci U S A , 100 :7877 , 2003
Abstract : Mycobacterium bovis is the causative agent of tuberculosis in a range of animal species and man, with worldwide annual losses to agriculture of $3 billion. The human burden of tuberculosis caused by the bovine tubercle bacillus is still largely unknown. M. bovis was also the progenitor for the M. bovis bacillus Calmette-Guerin vaccine strain, the most widely used human vaccine. Here we describe the 4,345,492-bp genome sequence of M. bovis AF2122/97 and its comparison with the genomes of Mycobacterium tuberculosis and Mycobacterium leprae. Strikingly, the genome sequence of M. bovis is >99.95% identical to that of M. tuberculosis, but deletion of genetic information has led to a reduced genome size. Comparison with M. leprae reveals a number of common gene losses, suggesting the removal of functional redundancy. Cell wall components and secreted proteins show the greatest variation, indicating their potential role in host-bacillus interactions or immune evasion. Furthermore, there are no genes unique to M. bovis, implying that differential gene expression may be the key to the host tropisms of human and bovine bacilli. The genome sequence therefore offers major insight on the evolution, host preference, and pathobiology of M. bovis.
ESTHER : Garnier_2003_Proc.Natl.Acad.Sci.U.S.A_100_7877
PubMedSearch : Garnier_2003_Proc.Natl.Acad.Sci.U.S.A_100_7877
PubMedID: 12788972
Gene_locus related to this paper: myctu-a85a , myctu-a85b , myctu-a85c , myctu-bpoC , myctu-cut3 , myctu-cutas1 , myctu-cutas2 , myctu-d5yk66 , myctu-ephB , myctu-ephc , myctu-ephd , myctu-ephE , myctu-hpx , myctu-linb , myctu-lipG , myctu-lipJ , myctu-LIPS , myctu-lipv , myctu-LPQC , myctu-LPQP , myctu-MBTB , myctu-metx , myctu-mpt51 , myctu-MT1628 , myctu-MT3441 , myctu-p71654 , myctu-p95011 , myctu-PKS6 , myctu-PKS13 , myctu-ppe42 , myctu-ppe63 , myctu-Rv1430 , myctu-RV0045C , myctu-Rv0077c , myctu-Rv0151c , myctu-Rv0152c , myctu-Rv0159c , myctu-Rv0160c , myctu-rv0183 , myctu-Rv0217c , myctu-Rv0220 , myctu-Rv0272c , myctu-RV0293C , myctu-RV0421C , myctu-RV0457C , myctu-RV0519C , myctu-RV0774C , myctu-RV0782 , myctu-RV0840C , myctu-Rv1069c , myctu-Rv1076 , myctu-RV1123C , myctu-Rv1184c , myctu-Rv1190 , myctu-Rv1191 , myctu-RV1192 , myctu-RV1215C , myctu-Rv1399c , myctu-Rv1400c , myctu-Rv1426c , myctu-RV1639C , myctu-RV1683 , myctu-RV1758 , myctu-Rv1800 , myctu-Rv1833c , myctu-Rv2045c , myctu-RV2054 , myctu-Rv2284 , myctu-RV2296 , myctu-Rv2385 , myctu-Rv2485c , myctu-RV2627C , myctu-RV2672 , myctu-RV2695 , myctu-RV2765 , myctu-RV2800 , myctu-RV2854 , myctu-Rv2970c , myctu-Rv3084 , myctu-Rv3097c , myctu-rv3177 , myctu-Rv3312c , myctu-RV3452 , myctu-RV3473C , myctu-Rv3487c , myctu-Rv3569c , myctu-RV3724 , myctu-Rv3802c , myctu-Rv3822 , myctu-y0571 , myctu-y963 , myctu-Y1834 , myctu-y1835 , myctu-y2079 , myctu-Y2307 , myctu-yc88 , myctu-ym23 , myctu-ym24 , myctu-YR15 , myctu-yt28