Genomic expression catalogue of a global collection of BCG vaccine strains show evidence for highly diverged metabolic and cell-wall adaptations.
Identifieur interne : 002750 ( PubMed/Curation ); précédent : 002749; suivant : 002751Genomic expression catalogue of a global collection of BCG vaccine strains show evidence for highly diverged metabolic and cell-wall adaptations.
Auteurs : Abdallah M. Abdallah ; Grant A. Hill-Cawthorne ; Thomas D. Otto [Royaume-Uni] ; Francesc Coll [Royaume-Uni] ; José Afonso Guerra-Assunção [Royaume-Uni] ; Ge Gao ; Raeece Naeem ; Hifzur Ansari ; Tareq B. Malas ; Sabir A. Adroub ; Theo Verboom [Pays-Bas] ; Roy Ummels [Pays-Bas] ; Huoming Zhang ; Aswini Kumar Panigrahi ; Ruth Mcnerney [Royaume-Uni] ; Roland Brosch [France] ; Taane G. Clark [Royaume-Uni] ; Marcel A. Behr [Canada] ; Wilbert Bitter [Pays-Bas] ; Arnab PainSource :
- Scientific reports [ 2045-2322 ] ; 2015.
Descripteurs français
- KwdFr :
- Acclimatation (génétique), Génome bactérien, Humains, Mycobacterium bovis (), Mycobacterium bovis (pathogénicité), Paroi cellulaire (), Paroi cellulaire (génétique), Phylogénie, Polymorphisme de nucléotide simple, Protéomique, Régulation de l'expression des gènes, Tuberculose (), Tuberculose (génétique), Tuberculose (microbiologie), Vaccin BCG (administration et posologie), Vaccin BCG (génétique), Variations de nombre de copies de segment d'ADN (génétique).
- MESH :
- administration et posologie : Vaccin BCG.
- génétique : Acclimatation, Paroi cellulaire, Tuberculose, Vaccin BCG, Variations de nombre de copies de segment d'ADN.
- microbiologie : Tuberculose.
- pathogénicité : Mycobacterium bovis.
- Génome bactérien, Humains, Mycobacterium bovis, Paroi cellulaire, Phylogénie, Polymorphisme de nucléotide simple, Protéomique, Régulation de l'expression des gènes, Tuberculose.
English descriptors
- KwdEn :
- Acclimatization (genetics), BCG Vaccine (administration & dosage), BCG Vaccine (genetics), Cell Wall (drug effects), Cell Wall (genetics), DNA Copy Number Variations (genetics), Gene Expression Regulation, Genome, Bacterial, Humans, Mycobacterium bovis (drug effects), Mycobacterium bovis (pathogenicity), Phylogeny, Polymorphism, Single Nucleotide, Proteomics, Tuberculosis (genetics), Tuberculosis (microbiology), Tuberculosis (prevention & control).
- MESH :
- chemical , administration & dosage : BCG Vaccine.
- drug effects : Cell Wall, Mycobacterium bovis.
- genetics : Acclimatization, BCG Vaccine, Cell Wall, DNA Copy Number Variations, Tuberculosis.
- microbiology : Tuberculosis.
- pathogenicity : Mycobacterium bovis.
- prevention & control : Tuberculosis.
- Gene Expression Regulation, Genome, Bacterial, Humans, Phylogeny, Polymorphism, Single Nucleotide, Proteomics.
Abstract
Although Bacillus Calmette-Guérin (BCG) vaccines against tuberculosis have been available for more than 90 years, their effectiveness has been hindered by variable protective efficacy and a lack of lasting memory responses. One factor contributing to this variability may be the diversity of the BCG strains that are used around the world, in part from genomic changes accumulated during vaccine production and their resulting differences in gene expression. We have compared the genomes and transcriptomes of a global collection of fourteen of the most widely used BCG strains at single base-pair resolution. We have also used quantitative proteomics to identify key differences in expression of proteins across five representative BCG strains of the four tandem duplication (DU) groups. We provide a comprehensive map of single nucleotide polymorphisms (SNPs), copy number variation and insertions and deletions (indels) across fourteen BCG strains. Genome-wide SNP characterization allowed the construction of a new and robust phylogenic genealogy of BCG strains. Transcriptional and proteomic profiling revealed a metabolic remodeling in BCG strains that may be reflected by altered immunogenicity and possibly vaccine efficacy. Together, these integrated-omic data represent the most comprehensive catalogue of genetic variation across a global collection of BCG strains.
DOI: 10.1038/srep15443
PubMed: 26487098
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Abdallah M. Abdallah<affiliation><nlm:affiliation>Pathogen Genomics Group, Biological, Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia.</nlm:affiliation><wicri:noCountry code="subField">Kingdom of Saudi Arabia</wicri:noCountry></affiliation><affiliation><nlm:affiliation>Pathogen Genomics Group, Biological, Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia.</nlm:affiliation><wicri:noCountry code="subField">Kingdom of Saudi Arabia</wicri:noCountry></affiliation><affiliation><nlm:affiliation>Pathogen Genomics Group, Biological, Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia.</nlm:affiliation><wicri:noCountry code="subField">Kingdom of Saudi Arabia</wicri:noCountry></affiliation><affiliation><nlm:affiliation>Pathogen Genomics Group, Biological, Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia.</nlm:affiliation><wicri:noCountry code="subField">Kingdom of Saudi Arabia</wicri:noCountry></affiliation><affiliation><nlm:affiliation>Pathogen Genomics Group, Biological, Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia.</nlm:affiliation><wicri:noCountry code="subField">Kingdom of Saudi Arabia</wicri:noCountry></affiliation><affiliation><nlm:affiliation>Computational Bioscience Research Center (CBRC), King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Jeddah, Kingdom of Saudi Arabia.</nlm:affiliation><wicri:noCountry code="subField">Kingdom of Saudi Arabia</wicri:noCountry></affiliation><affiliation><nlm:affiliation>Pathogen Genomics Group, Biological, Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia.</nlm:affiliation><wicri:noCountry code="subField">Kingdom of Saudi Arabia</wicri:noCountry></affiliation><affiliation><nlm:affiliation>Bioscience Core Laboratory, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia.</nlm:affiliation><wicri:noCountry code="subField">Kingdom of Saudi Arabia</wicri:noCountry></affiliation><affiliation><nlm:affiliation>Bioscience Core Laboratory, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia.</nlm:affiliation><wicri:noCountry code="subField">Kingdom of Saudi Arabia</wicri:noCountry></affiliation><affiliation><nlm:affiliation>Pathogen Genomics Group, Biological, Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia.</nlm:affiliation><wicri:noCountry code="subField">Kingdom of Saudi Arabia</wicri:noCountry></affiliation>Le document en format XML
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Clark</name><affiliation wicri:level="1"><nlm:affiliation>Faculty of Infectious and Tropical Diseases, London School of Hygiene &Tropical Medicine, London, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Faculty of Infectious and Tropical Diseases, London School of Hygiene &Tropical Medicine, London</wicri:regionArea></affiliation></author><author><name sortKey="Behr, Marcel A" sort="Behr, Marcel A" uniqKey="Behr M" first="Marcel A" last="Behr">Marcel A. Behr</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, McGill University Health Centre, Montreal, QC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Medicine, McGill University Health Centre, Montreal, QC</wicri:regionArea></affiliation></author><author><name sortKey="Bitter, Wilbert" sort="Bitter, Wilbert" uniqKey="Bitter W" first="Wilbert" last="Bitter">Wilbert Bitter</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Microbiology and Infection Control, VU University Medical Center, 1081 BT Amsterdam, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Medical Microbiology and Infection Control, VU University Medical Center, 1081 BT Amsterdam</wicri:regionArea></affiliation></author><author><name sortKey="Pain, Arnab" sort="Pain, Arnab" uniqKey="Pain A" first="Arnab" last="Pain">Arnab Pain</name><affiliation><nlm:affiliation>Pathogen Genomics Group, Biological, Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia.</nlm:affiliation><wicri:noCountry code="subField">Kingdom of Saudi Arabia</wicri:noCountry></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2015">2015</date><idno type="RBID">pubmed:26487098</idno><idno type="pmid">26487098</idno><idno type="doi">10.1038/srep15443</idno><idno type="wicri:Area/PubMed/Corpus">002819</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002819</idno><idno type="wicri:Area/PubMed/Curation">002750</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002750</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Genomic expression catalogue of a global collection of BCG vaccine strains show evidence for highly diverged metabolic and cell-wall adaptations.</title><author><name sortKey="Abdallah, Abdallah M" sort="Abdallah, Abdallah M" uniqKey="Abdallah A" first="Abdallah M" last="Abdallah">Abdallah M. Abdallah</name><affiliation><nlm:affiliation>Pathogen Genomics Group, Biological, Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia.</nlm:affiliation><wicri:noCountry code="subField">Kingdom of Saudi Arabia</wicri:noCountry></affiliation></author><author><name sortKey="Hill Cawthorne, Grant A" sort="Hill Cawthorne, Grant A" uniqKey="Hill Cawthorne G" first="Grant A" last="Hill-Cawthorne">Grant A. Hill-Cawthorne</name><affiliation><nlm:affiliation>Pathogen Genomics Group, Biological, Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia.</nlm:affiliation><wicri:noCountry code="subField">Kingdom of Saudi Arabia</wicri:noCountry></affiliation></author><author><name sortKey="Otto, Thomas D" sort="Otto, Thomas D" uniqKey="Otto T" first="Thomas D" last="Otto">Thomas D. Otto</name><affiliation wicri:level="1"><nlm:affiliation>Pathogen Genomics, The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Pathogen Genomics, The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA</wicri:regionArea></affiliation></author><author><name sortKey="Coll, Francesc" sort="Coll, Francesc" uniqKey="Coll F" first="Francesc" last="Coll">Francesc Coll</name><affiliation wicri:level="1"><nlm:affiliation>Faculty of Infectious and Tropical Diseases, London School of Hygiene &Tropical Medicine, London, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Faculty of Infectious and Tropical Diseases, London School of Hygiene &Tropical Medicine, London</wicri:regionArea></affiliation></author><author><name sortKey="Guerra Assuncao, Jose Afonso" sort="Guerra Assuncao, Jose Afonso" uniqKey="Guerra Assuncao J" first="José Afonso" last="Guerra-Assunção">José Afonso Guerra-Assunção</name><affiliation wicri:level="1"><nlm:affiliation>Faculty of Infectious and Tropical Diseases, London School of Hygiene &Tropical Medicine, London, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Faculty of Infectious and Tropical Diseases, London School of Hygiene &Tropical Medicine, London</wicri:regionArea></affiliation></author><author><name sortKey="Gao, Ge" sort="Gao, Ge" uniqKey="Gao G" first="Ge" last="Gao">Ge Gao</name><affiliation><nlm:affiliation>Pathogen Genomics Group, Biological, Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia.</nlm:affiliation><wicri:noCountry code="subField">Kingdom of Saudi Arabia</wicri:noCountry></affiliation></author><author><name sortKey="Naeem, Raeece" sort="Naeem, Raeece" uniqKey="Naeem R" first="Raeece" last="Naeem">Raeece Naeem</name><affiliation><nlm:affiliation>Pathogen Genomics Group, Biological, Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia.</nlm:affiliation><wicri:noCountry code="subField">Kingdom of Saudi Arabia</wicri:noCountry></affiliation></author><author><name sortKey="Ansari, Hifzur" sort="Ansari, Hifzur" uniqKey="Ansari H" first="Hifzur" last="Ansari">Hifzur Ansari</name><affiliation><nlm:affiliation>Pathogen Genomics Group, Biological, Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia.</nlm:affiliation><wicri:noCountry code="subField">Kingdom of Saudi Arabia</wicri:noCountry></affiliation></author><author><name sortKey="Malas, Tareq B" sort="Malas, Tareq B" uniqKey="Malas T" first="Tareq B" last="Malas">Tareq B. Malas</name><affiliation><nlm:affiliation>Computational Bioscience Research Center (CBRC), King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Jeddah, Kingdom of Saudi Arabia.</nlm:affiliation><wicri:noCountry code="subField">Kingdom of Saudi Arabia</wicri:noCountry></affiliation></author><author><name sortKey="Adroub, Sabir A" sort="Adroub, Sabir A" uniqKey="Adroub S" first="Sabir A" last="Adroub">Sabir A. Adroub</name><affiliation><nlm:affiliation>Pathogen Genomics Group, Biological, Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia.</nlm:affiliation><wicri:noCountry code="subField">Kingdom of Saudi Arabia</wicri:noCountry></affiliation></author><author><name sortKey="Verboom, Theo" sort="Verboom, Theo" uniqKey="Verboom T" first="Theo" last="Verboom">Theo Verboom</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Microbiology and Infection Control, VU University Medical Center, 1081 BT Amsterdam, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Medical Microbiology and Infection Control, VU University Medical Center, 1081 BT Amsterdam</wicri:regionArea></affiliation></author><author><name sortKey="Ummels, Roy" sort="Ummels, Roy" uniqKey="Ummels R" first="Roy" last="Ummels">Roy Ummels</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Microbiology and Infection Control, VU University Medical Center, 1081 BT Amsterdam, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Medical Microbiology and Infection Control, VU University Medical Center, 1081 BT Amsterdam</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Huoming" sort="Zhang, Huoming" uniqKey="Zhang H" first="Huoming" last="Zhang">Huoming Zhang</name><affiliation><nlm:affiliation>Bioscience Core Laboratory, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia.</nlm:affiliation><wicri:noCountry code="subField">Kingdom of Saudi Arabia</wicri:noCountry></affiliation></author><author><name sortKey="Panigrahi, Aswini Kumar" sort="Panigrahi, Aswini Kumar" uniqKey="Panigrahi A" first="Aswini Kumar" last="Panigrahi">Aswini Kumar Panigrahi</name><affiliation><nlm:affiliation>Bioscience Core Laboratory, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia.</nlm:affiliation><wicri:noCountry code="subField">Kingdom of Saudi Arabia</wicri:noCountry></affiliation></author><author><name sortKey="Mcnerney, Ruth" sort="Mcnerney, Ruth" uniqKey="Mcnerney R" first="Ruth" last="Mcnerney">Ruth Mcnerney</name><affiliation wicri:level="1"><nlm:affiliation>Faculty of Infectious and Tropical Diseases, London School of Hygiene &Tropical Medicine, London, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Faculty of Infectious and Tropical Diseases, London School of Hygiene &Tropical Medicine, London</wicri:regionArea></affiliation></author><author><name sortKey="Brosch, Roland" sort="Brosch, Roland" uniqKey="Brosch R" first="Roland" last="Brosch">Roland Brosch</name><affiliation wicri:level="1"><nlm:affiliation>Institut Pasteur, Unit for Integrated Mycobacterial Pathogenomics, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut Pasteur, Unit for Integrated Mycobacterial Pathogenomics, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Clark, Taane G" sort="Clark, Taane G" uniqKey="Clark T" first="Taane G" last="Clark">Taane G. Clark</name><affiliation wicri:level="1"><nlm:affiliation>Faculty of Infectious and Tropical Diseases, London School of Hygiene &Tropical Medicine, London, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Faculty of Infectious and Tropical Diseases, London School of Hygiene &Tropical Medicine, London</wicri:regionArea></affiliation></author><author><name sortKey="Behr, Marcel A" sort="Behr, Marcel A" uniqKey="Behr M" first="Marcel A" last="Behr">Marcel A. Behr</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, McGill University Health Centre, Montreal, QC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Medicine, McGill University Health Centre, Montreal, QC</wicri:regionArea></affiliation></author><author><name sortKey="Bitter, Wilbert" sort="Bitter, Wilbert" uniqKey="Bitter W" first="Wilbert" last="Bitter">Wilbert Bitter</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Microbiology and Infection Control, VU University Medical Center, 1081 BT Amsterdam, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Medical Microbiology and Infection Control, VU University Medical Center, 1081 BT Amsterdam</wicri:regionArea></affiliation></author><author><name sortKey="Pain, Arnab" sort="Pain, Arnab" uniqKey="Pain A" first="Arnab" last="Pain">Arnab Pain</name><affiliation><nlm:affiliation>Pathogen Genomics Group, Biological, Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia.</nlm:affiliation><wicri:noCountry code="subField">Kingdom of Saudi Arabia</wicri:noCountry></affiliation></author></analytic><series><title level="j">Scientific reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Acclimatization (genetics)</term><term>BCG Vaccine (administration & dosage)</term><term>BCG Vaccine (genetics)</term><term>Cell Wall (drug effects)</term><term>Cell Wall (genetics)</term><term>DNA Copy Number Variations (genetics)</term><term>Gene Expression Regulation</term><term>Genome, Bacterial</term><term>Humans</term><term>Mycobacterium bovis (drug effects)</term><term>Mycobacterium bovis (pathogenicity)</term><term>Phylogeny</term><term>Polymorphism, Single Nucleotide</term><term>Proteomics</term><term>Tuberculosis (genetics)</term><term>Tuberculosis (microbiology)</term><term>Tuberculosis (prevention & control)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Acclimatation (génétique)</term><term>Génome bactérien</term><term>Humains</term><term>Mycobacterium bovis ()</term><term>Mycobacterium bovis (pathogénicité)</term><term>Paroi cellulaire ()</term><term>Paroi cellulaire (génétique)</term><term>Phylogénie</term><term>Polymorphisme de nucléotide simple</term><term>Protéomique</term><term>Régulation de l'expression des gènes</term><term>Tuberculose ()</term><term>Tuberculose (génétique)</term><term>Tuberculose (microbiologie)</term><term>Vaccin BCG (administration et posologie)</term><term>Vaccin BCG (génétique)</term><term>Variations de nombre de copies de segment d'ADN (génétique)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>BCG Vaccine</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Vaccin BCG</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cell Wall</term><term>Mycobacterium bovis</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Acclimatization</term><term>BCG Vaccine</term><term>Cell Wall</term><term>DNA Copy Number Variations</term><term>Tuberculosis</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Acclimatation</term><term>Paroi cellulaire</term><term>Tuberculose</term><term>Vaccin BCG</term><term>Variations de nombre de copies de segment d'ADN</term></keywords><keywords scheme="MESH" qualifier="microbiologie" xml:lang="fr"><term>Tuberculose</term></keywords><keywords scheme="MESH" qualifier="microbiology" xml:lang="en"><term>Tuberculosis</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Mycobacterium bovis</term></keywords><keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Mycobacterium bovis</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Tuberculosis</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Gene Expression Regulation</term><term>Genome, Bacterial</term><term>Humans</term><term>Phylogeny</term><term>Polymorphism, Single Nucleotide</term><term>Proteomics</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Génome bactérien</term><term>Humains</term><term>Mycobacterium bovis</term><term>Paroi cellulaire</term><term>Phylogénie</term><term>Polymorphisme de nucléotide simple</term><term>Protéomique</term><term>Régulation de l'expression des gènes</term><term>Tuberculose</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Although Bacillus Calmette-Guérin (BCG) vaccines against tuberculosis have been available for more than 90 years, their effectiveness has been hindered by variable protective efficacy and a lack of lasting memory responses. One factor contributing to this variability may be the diversity of the BCG strains that are used around the world, in part from genomic changes accumulated during vaccine production and their resulting differences in gene expression. We have compared the genomes and transcriptomes of a global collection of fourteen of the most widely used BCG strains at single base-pair resolution. We have also used quantitative proteomics to identify key differences in expression of proteins across five representative BCG strains of the four tandem duplication (DU) groups. We provide a comprehensive map of single nucleotide polymorphisms (SNPs), copy number variation and insertions and deletions (indels) across fourteen BCG strains. Genome-wide SNP characterization allowed the construction of a new and robust phylogenic genealogy of BCG strains. Transcriptional and proteomic profiling revealed a metabolic remodeling in BCG strains that may be reflected by altered immunogenicity and possibly vaccine efficacy. Together, these integrated-omic data represent the most comprehensive catalogue of genetic variation across a global collection of BCG strains.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">26487098</PMID><DateCreated><Year>2015</Year><Month>10</Month><Day>21</Day></DateCreated><DateCompleted><Year>2016</Year><Month>09</Month><Day>14</Day></DateCompleted><DateRevised><Year>2017</Year><Month>02</Month><Day>20</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">2045-2322</ISSN><JournalIssue CitedMedium="Internet"><Volume>5</Volume><PubDate><Year>2015</Year><Month>Oct</Month><Day>21</Day></PubDate></JournalIssue><Title>Scientific reports</Title><ISOAbbreviation>Sci Rep</ISOAbbreviation></Journal><ArticleTitle>Genomic expression catalogue of a global collection of BCG vaccine strains show evidence for highly diverged metabolic and cell-wall adaptations.</ArticleTitle><Pagination><MedlinePgn>15443</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/srep15443</ELocationID><Abstract><AbstractText>Although Bacillus Calmette-Guérin (BCG) vaccines against tuberculosis have been available for more than 90 years, their effectiveness has been hindered by variable protective efficacy and a lack of lasting memory responses. One factor contributing to this variability may be the diversity of the BCG strains that are used around the world, in part from genomic changes accumulated during vaccine production and their resulting differences in gene expression. We have compared the genomes and transcriptomes of a global collection of fourteen of the most widely used BCG strains at single base-pair resolution. We have also used quantitative proteomics to identify key differences in expression of proteins across five representative BCG strains of the four tandem duplication (DU) groups. We provide a comprehensive map of single nucleotide polymorphisms (SNPs), copy number variation and insertions and deletions (indels) across fourteen BCG strains. Genome-wide SNP characterization allowed the construction of a new and robust phylogenic genealogy of BCG strains. Transcriptional and proteomic profiling revealed a metabolic remodeling in BCG strains that may be reflected by altered immunogenicity and possibly vaccine efficacy. Together, these integrated-omic data represent the most comprehensive catalogue of genetic variation across a global collection of BCG strains.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Abdallah</LastName><ForeName>Abdallah M</ForeName><Initials>AM</Initials><AffiliationInfo><Affiliation>Pathogen Genomics Group, Biological, Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hill-Cawthorne</LastName><ForeName>Grant A</ForeName><Initials>GA</Initials><AffiliationInfo><Affiliation>Pathogen Genomics Group, Biological, Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Marie Bashir Institute for Infectious Diseases and Biosecurity and School and Public Health, University of Sydney, NSW 2006, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Otto</LastName><ForeName>Thomas D</ForeName><Initials>TD</Initials><AffiliationInfo><Affiliation>Pathogen Genomics, The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Coll</LastName><ForeName>Francesc</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Faculty of Infectious and Tropical Diseases, London School of Hygiene &Tropical Medicine, London, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Guerra-Assunção</LastName><ForeName>José Afonso</ForeName><Initials>JA</Initials><AffiliationInfo><Affiliation>Faculty of Infectious and Tropical Diseases, London School of Hygiene &Tropical Medicine, London, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gao</LastName><ForeName>Ge</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Pathogen Genomics Group, Biological, Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Naeem</LastName><ForeName>Raeece</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Pathogen Genomics Group, Biological, Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ansari</LastName><ForeName>Hifzur</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Pathogen Genomics Group, Biological, Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Malas</LastName><ForeName>Tareq B</ForeName><Initials>TB</Initials><AffiliationInfo><Affiliation>Computational Bioscience Research Center (CBRC), King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Jeddah, Kingdom of Saudi Arabia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Adroub</LastName><ForeName>Sabir A</ForeName><Initials>SA</Initials><AffiliationInfo><Affiliation>Pathogen Genomics Group, Biological, Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Verboom</LastName><ForeName>Theo</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Department of Medical Microbiology and Infection Control, VU University Medical Center, 1081 BT Amsterdam, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ummels</LastName><ForeName>Roy</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Department of Medical Microbiology and Infection Control, VU University Medical Center, 1081 BT Amsterdam, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Huoming</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Bioscience Core Laboratory, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Panigrahi</LastName><ForeName>Aswini Kumar</ForeName><Initials>AK</Initials><AffiliationInfo><Affiliation>Bioscience Core Laboratory, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>McNerney</LastName><ForeName>Ruth</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Faculty of Infectious and Tropical Diseases, London School of Hygiene &Tropical Medicine, London, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Brosch</LastName><ForeName>Roland</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Institut Pasteur, Unit for Integrated Mycobacterial Pathogenomics, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Clark</LastName><ForeName>Taane G</ForeName><Initials>TG</Initials><AffiliationInfo><Affiliation>Faculty of Infectious and Tropical Diseases, London School of Hygiene &Tropical Medicine, London, United Kingdom.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Behr</LastName><ForeName>Marcel A</ForeName><Initials>MA</Initials><AffiliationInfo><Affiliation>Department of Medicine, McGill University Health Centre, Montreal, QC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bitter</LastName><ForeName>Wilbert</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Department of Medical Microbiology and Infection Control, VU University Medical Center, 1081 BT Amsterdam, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pain</LastName><ForeName>Arnab</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Pathogen Genomics Group, Biological, Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, 001-0020, Japan.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>MR/K000551/1</GrantID><Agency>Medical Research Council</Agency><Country>United Kingdom</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2015</Year><Month>10</Month><Day>21</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Sci Rep</MedlineTA><NlmUniqueID>101563288</NlmUniqueID><ISSNLinking>2045-2322</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D001500">BCG Vaccine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections 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RefType="Cites"><RefSource>Crit Rev Oncol Hematol. 2002 Oct;44(1):81-102</RefSource><PMID Version="1">12399001</PMID></CommentsCorrections></CommentsCorrectionsList><MeshHeadingList><MeshHeading><DescriptorName UI="D000064" MajorTopicYN="N">Acclimatization</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001500" MajorTopicYN="N">BCG Vaccine</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002473" MajorTopicYN="N">Cell Wall</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D056915" MajorTopicYN="N">DNA Copy Number Variations</DescriptorName><QualifierName UI="Q000235" 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