Genome plasticity of BCG and impact on vaccine efficacy. Export

@article{citeulike:1543546, abstract = {To understand the evolution, attenuation, and variable protective efficacy of bacillus Calmette-Gu\'{e}rin (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.}, address = {Unit\'{e} de G\'{e}n\'{e}tique Mol\'{e}culaire Bact\'{e}rienne, Institut Pasteur, 28 Rue du Docteur Roux, 75724 Paris Cedex 15, France.}, author = {Brosch, R. and Gordon, S. V. and Garnier, T. and Eiglmeier, K. and Frigui, W. and Valenti, P. and Dos Santos, S. and Duthoy, S. and Lacroix, C. and Garcia-Pelayo, C. and Inwald, J. K. and Golby, P. and Garcia, J. N. and Hewinson, R. G. and Behr, M. A. and Quail, M. A. and Churcher, C. and Barrell, B. G. and Parkhill, J. and Cole, S. T.}, citeulike-article-id = {1543546}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0700869104}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/17372194}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=17372194}, day = {27}, doi = {10.1073/pnas.0700869104}, issn = {0027-8424}, journal = {Proc Natl Acad Sci U S A}, keywords = {bcg, efficacy, genome, tb, tuberculosis, vaccine}, month = {March}, number = {13}, pages = {5596--5601}, posted-at = {2007-08-08 16:44:15}, priority = {2}, title = {Genome plasticity of BCG and impact on vaccine efficacy.}, url = {http://dx.doi.org/10.1073/pnas.0700869104}, volume = {104}, year = {2007} }

TY - JOUR ID - citeulike:1543546 L3 - citeulike-article-id:1543546 N2 - To understand the evolution, attenuation, and variable protective efficacy of bacillus Calmette-Guérin (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. IS - 13 JF - Proc Natl Acad Sci U S A SN - 0027-8424 AD - Unité de Génétique Moléculaire Bactérienne, Institut Pasteur, 28 Rue du Docteur Roux, 75724 Paris Cedex 15, France. EP - 5601 TI - Genome plasticity of BCG and impact on vaccine efficacy. VL - 104 SP - 5596 KW - bcg KW - efficacy KW - genome KW - tb KW - tuberculosis KW - vaccine AU - Brosch, R AU - Gordon, SV AU - Garnier, T AU - Eiglmeier, K AU - Frigui, W AU - Valenti, P AU - Dos Santos, S AU - Duthoy, S AU - Lacroix, C AU - Garcia-Pelayo, C AU - Inwald, JK AU - Golby, P AU - Garcia, JN AU - Hewinson, RG AU - Behr, MA AU - Quail, MA AU - Churcher, C AU - Barrell, BG AU - Parkhill, J AU - Cole, ST PY - 2007/03/27/ UR - http://dx.doi.org/10.1073/pnas.0700869104 ER -