Significant under expression of the DosR regulon in M. tuberculosis complex lineage 6 in sputum.
Identifieur interne : 000787 ( PubMed/Curation ); précédent : 000786; suivant : 000788Significant under expression of the DosR regulon in M. tuberculosis complex lineage 6 in sputum.
Auteurs : Boatema Ofori-Anyinam [Gambie] ; Gregory Dolganov [États-Unis] ; Tran Van [États-Unis] ; J Lucian Davis [États-Unis] ; Nicholas D. Walter [États-Unis] ; Benjamin J. Garcia [États-Unis] ; Marty Voskuil [États-Unis] ; Kristina Fissette [Belgique] ; Maren Diels [Belgique] ; Michèle Driesen [Belgique] ; Conor J. Meehan [Belgique] ; Dorothy Yeboah-Manu [Ghana] ; Mireia Coscolla [Suisse] ; Sebastien Gagneux [Suisse] ; Martin Antonio [Gambie] ; Gary Schoolnik [États-Unis] ; Florian Gehre [Gambie] ; Bouke C. De Jong [Belgique]Source :
- Tuberculosis (Edinburgh, Scotland) [ 1873-281X ] ; 2017.
Abstract
Mycobacterium africanum lineage (L) 6 is an important pathogen in West Africa, causing up to 40% of pulmonary tuberculosis (TB). The biology underlying the clinical differences between M. africanum and M. tuberculosis sensu stricto remains poorly understood. We performed ex vivo expression of 2179 genes of the most geographically dispersed cause of human TB, M. tuberculosis L4 and the geographically restricted, M. africanum L6 directly from sputa of 11 HIV-negative TB patients from The Gambia who had not started treatment. The DosR regulon was the most significantly decreased category in L6 relative to L4. Further, we identified nonsynonymous mutations in major DosR regulon genes of 44 L6 genomes of TB patients from The Gambia and Ghana. Using Lebek's test, we assessed differences in oxygen requirements for growth. L4 grew only at the aerobic surface while L6 grew throughout the medium. In the host, the DosR regulon is critical for M. tuberculosis in adaptation to oxygen limitation. However, M. africanum L6 appears to have adapted to growth under hypoxic conditions or to different biological niches. The observed under expression of DosR in L6 fits with the genomic changes in DosR genes, microaerobic growth and the association with extrapulmonary disease.
DOI: 10.1016/j.tube.2017.03.001
PubMed: 28454650
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Box 273, Banjul</wicri:regionArea></affiliation></author><author><name sortKey="Dolganov, Gregory" sort="Dolganov, Gregory" uniqKey="Dolganov G" first="Gregory" last="Dolganov">Gregory Dolganov</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, Stanford University, 299 Campus Drive, Stanford, CA, 94305, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Stanford University, 299 Campus Drive, Stanford, CA, 94305</wicri:regionArea></affiliation></author><author><name sortKey="Van, Tran" sort="Van, Tran" uniqKey="Van T" first="Tran" last="Van">Tran Van</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, Stanford University, 299 Campus Drive, Stanford, CA, 94305, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Stanford University, 299 Campus Drive, Stanford, CA, 94305</wicri:regionArea></affiliation></author><author><name sortKey="Davis, J Lucian" sort="Davis, J Lucian" uniqKey="Davis J" first="J Lucian" last="Davis">J Lucian Davis</name><affiliation wicri:level="1"><nlm:affiliation>Department of Epidemiology of Microbial Diseases, Yale School of Public Health, 60 College Street, P.O. Box 208034, New Haven, CT, 06520-8034, USA; Department of Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, P.O. Box 208057, 300 Cedar Street TAC - 441 South, New Haven, CT, 06520-8057, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology of Microbial Diseases, Yale School of Public Health, 60 College Street, P.O. Box 208034, New Haven, CT, 06520-8034, USA; Department of Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, P.O. Box 208057, 300 Cedar Street TAC - 441 South, New Haven, CT, 06520-8057</wicri:regionArea></affiliation></author><author><name sortKey="Walter, Nicholas D" sort="Walter, Nicholas D" uniqKey="Walter N" first="Nicholas D" last="Walter">Nicholas D. Walter</name><affiliation wicri:level="1"><nlm:affiliation>Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Denver, Building 500 - 13001 E, 17th Place, Campus Box C290, Aurora, CO, 80045, USA; Pulmonary Section, Denver Veterans Affairs Medical Center, 1055 Clermont Street, Denver, CO, 80220, USA; Integrated Center for Genes, Environment, & Health, National Jewish Health, Smith Building; A647, 1400 Jackson Street, Denver, CO, 80206, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Denver, Building 500 - 13001 E, 17th Place, Campus Box C290, Aurora, CO, 80045, USA; Pulmonary Section, Denver Veterans Affairs Medical Center, 1055 Clermont Street, Denver, CO, 80220, USA; Integrated Center for Genes, Environment, & Health, National Jewish Health, Smith Building; A647, 1400 Jackson Street, Denver, CO, 80206</wicri:regionArea></affiliation></author><author><name sortKey="Garcia, Benjamin J" sort="Garcia, Benjamin J" uniqKey="Garcia B" first="Benjamin J" last="Garcia">Benjamin J. Garcia</name><affiliation wicri:level="1"><nlm:affiliation>Integrated Center for Genes, Environment, & Health, National Jewish Health, Smith Building; A647, 1400 Jackson Street, Denver, CO, 80206, USA; Computational Bioscience Program, University of Colorado Denver, Building 500 - 13001 E, 17th Place, Campus Box C290, Aurora, CO, 80045, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Integrated Center for Genes, Environment, & Health, National Jewish Health, Smith Building; A647, 1400 Jackson Street, Denver, CO, 80206, USA; Computational Bioscience Program, University of Colorado Denver, Building 500 - 13001 E, 17th Place, Campus Box C290, Aurora, CO, 80045</wicri:regionArea></affiliation></author><author><name sortKey="Voskuil, Marty" sort="Voskuil, Marty" uniqKey="Voskuil M" first="Marty" last="Voskuil">Marty Voskuil</name><affiliation wicri:level="1"><nlm:affiliation>Department of Immunology and Microbiology, University of Colorado School of Medicine, 12800 E. 19th Ave., Mail Stop 8333, Aurora, CO, 80045, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Immunology and Microbiology, University of Colorado School of Medicine, 12800 E. 19th Ave., Mail Stop 8333, Aurora, CO, 80045</wicri:regionArea></affiliation></author><author><name sortKey="Fissette, Kristina" sort="Fissette, Kristina" uniqKey="Fissette K" first="Kristina" last="Fissette">Kristina Fissette</name><affiliation wicri:level="1"><nlm:affiliation>Mycobacteriology Unit, Institute of Tropical Medicine (ITM), Nationalestraat 155, 2000, Antwerp, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Mycobacteriology Unit, Institute of Tropical Medicine (ITM), Nationalestraat 155, 2000, Antwerp</wicri:regionArea></affiliation></author><author><name sortKey="Diels, Maren" sort="Diels, Maren" uniqKey="Diels M" first="Maren" last="Diels">Maren Diels</name><affiliation wicri:level="1"><nlm:affiliation>Mycobacteriology Unit, Institute of Tropical Medicine (ITM), Nationalestraat 155, 2000, Antwerp, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Mycobacteriology Unit, Institute of Tropical Medicine (ITM), Nationalestraat 155, 2000, Antwerp</wicri:regionArea></affiliation></author><author><name sortKey="Driesen, Michele" sort="Driesen, Michele" uniqKey="Driesen M" first="Michèle" last="Driesen">Michèle Driesen</name><affiliation wicri:level="1"><nlm:affiliation>Mycobacteriology Unit, Institute of Tropical Medicine (ITM), Nationalestraat 155, 2000, Antwerp, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Mycobacteriology Unit, Institute of Tropical Medicine (ITM), Nationalestraat 155, 2000, Antwerp</wicri:regionArea></affiliation></author><author><name sortKey="Meehan, Conor J" sort="Meehan, Conor J" uniqKey="Meehan C" first="Conor J" last="Meehan">Conor J. Meehan</name><affiliation wicri:level="1"><nlm:affiliation>Mycobacteriology Unit, Institute of Tropical Medicine (ITM), Nationalestraat 155, 2000, Antwerp, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Mycobacteriology Unit, Institute of Tropical Medicine (ITM), Nationalestraat 155, 2000, Antwerp</wicri:regionArea></affiliation></author><author><name sortKey="Yeboah Manu, Dorothy" sort="Yeboah Manu, Dorothy" uniqKey="Yeboah Manu D" first="Dorothy" last="Yeboah-Manu">Dorothy Yeboah-Manu</name><affiliation wicri:level="1"><nlm:affiliation>Noguchi Memorial Institute for Medical Research, University of Ghana, P.O. Box LG 581, Legon, Accra, Ghana.</nlm:affiliation><country xml:lang="fr">Ghana</country><wicri:regionArea>Noguchi Memorial Institute for Medical Research, University of Ghana, P.O. Box LG 581, Legon, Accra</wicri:regionArea></affiliation></author><author><name sortKey="Coscolla, Mireia" sort="Coscolla, Mireia" uniqKey="Coscolla M" first="Mireia" last="Coscolla">Mireia Coscolla</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, P.O. Box 4002, Basel, Switzerland; University of Basel, Petersplatz 1, P.O. Box 4001, Basel, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, P.O. Box 4002, Basel, Switzerland; University of Basel, Petersplatz 1, P.O. Box 4001, Basel</wicri:regionArea></affiliation></author><author><name sortKey="Gagneux, Sebastien" sort="Gagneux, Sebastien" uniqKey="Gagneux S" first="Sebastien" last="Gagneux">Sebastien Gagneux</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, P.O. Box 4002, Basel, Switzerland; University of Basel, Petersplatz 1, P.O. Box 4001, Basel, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, P.O. Box 4002, Basel, Switzerland; University of Basel, Petersplatz 1, P.O. Box 4001, Basel</wicri:regionArea></affiliation></author><author><name sortKey="Antonio, Martin" sort="Antonio, Martin" uniqKey="Antonio M" first="Martin" last="Antonio">Martin Antonio</name><affiliation wicri:level="1"><nlm:affiliation>Vaccines and Immunity Theme, Medical Research Council (MRC) Unit, The Gambia, Atlantic Boulevard, Fajara, P.O. Box 273, Banjul, Gambia.</nlm:affiliation><country xml:lang="fr">Gambie</country><wicri:regionArea>Vaccines and Immunity Theme, Medical Research Council (MRC) Unit, The Gambia, Atlantic Boulevard, Fajara, P.O. Box 273, Banjul</wicri:regionArea></affiliation></author><author><name sortKey="Schoolnik, Gary" sort="Schoolnik, Gary" uniqKey="Schoolnik G" first="Gary" last="Schoolnik">Gary Schoolnik</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, Stanford University, 299 Campus Drive, Stanford, CA, 94305, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Stanford University, 299 Campus Drive, Stanford, CA, 94305</wicri:regionArea></affiliation></author><author><name sortKey="Gehre, Florian" sort="Gehre, Florian" uniqKey="Gehre F" first="Florian" last="Gehre">Florian Gehre</name><affiliation wicri:level="1"><nlm:affiliation>Mycobacteriology Unit, Institute of Tropical Medicine (ITM), Nationalestraat 155, 2000, Antwerp, Belgium; Vaccines and Immunity Theme, Medical Research Council (MRC) Unit, The Gambia, Atlantic Boulevard, Fajara, P.O. Box 273, Banjul, Gambia.</nlm:affiliation><country xml:lang="fr">Gambie</country><wicri:regionArea>Mycobacteriology Unit, Institute of Tropical Medicine (ITM), Nationalestraat 155, 2000, Antwerp, Belgium; Vaccines and Immunity Theme, Medical Research Council (MRC) Unit, The Gambia, Atlantic Boulevard, Fajara, P.O. Box 273, Banjul</wicri:regionArea></affiliation></author><author><name sortKey="De Jong, Bouke C" sort="De Jong, Bouke C" uniqKey="De Jong B" first="Bouke C" last="De Jong">Bouke C. De Jong</name><affiliation wicri:level="1"><nlm:affiliation>Mycobacteriology Unit, Institute of Tropical Medicine (ITM), Nationalestraat 155, 2000, Antwerp, Belgium. Electronic address: bdejong@itg.be.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Mycobacteriology Unit, Institute of Tropical Medicine (ITM), Nationalestraat 155, 2000, Antwerp</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2017">2017</date><idno type="RBID">pubmed:28454650</idno><idno type="pmid">28454650</idno><idno type="doi">10.1016/j.tube.2017.03.001</idno><idno type="wicri:Area/PubMed/Corpus">000787</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000787</idno><idno type="wicri:Area/PubMed/Curation">000787</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000787</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Significant under expression of the DosR regulon in M. tuberculosis complex lineage 6 in sputum.</title><author><name sortKey="Ofori Anyinam, Boatema" sort="Ofori Anyinam, Boatema" uniqKey="Ofori Anyinam B" first="Boatema" last="Ofori-Anyinam">Boatema Ofori-Anyinam</name><affiliation wicri:level="1"><nlm:affiliation>Mycobacteriology Unit, Institute of Tropical Medicine (ITM), Nationalestraat 155, 2000, Antwerp, Belgium; Vaccines and Immunity Theme, Medical Research Council (MRC) Unit, The Gambia, Atlantic Boulevard, Fajara, P.O. Box 273, Banjul, Gambia.</nlm:affiliation><country xml:lang="fr">Gambie</country><wicri:regionArea>Mycobacteriology Unit, Institute of Tropical Medicine (ITM), Nationalestraat 155, 2000, Antwerp, Belgium; Vaccines and Immunity Theme, Medical Research Council (MRC) Unit, The Gambia, Atlantic Boulevard, Fajara, P.O. Box 273, Banjul</wicri:regionArea></affiliation></author><author><name sortKey="Dolganov, Gregory" sort="Dolganov, Gregory" uniqKey="Dolganov G" first="Gregory" last="Dolganov">Gregory Dolganov</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, Stanford University, 299 Campus Drive, Stanford, CA, 94305, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Stanford University, 299 Campus Drive, Stanford, CA, 94305</wicri:regionArea></affiliation></author><author><name sortKey="Van, Tran" sort="Van, Tran" uniqKey="Van T" first="Tran" last="Van">Tran Van</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, Stanford University, 299 Campus Drive, Stanford, CA, 94305, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Stanford University, 299 Campus Drive, Stanford, CA, 94305</wicri:regionArea></affiliation></author><author><name sortKey="Davis, J Lucian" sort="Davis, J Lucian" uniqKey="Davis J" first="J Lucian" last="Davis">J Lucian Davis</name><affiliation wicri:level="1"><nlm:affiliation>Department of Epidemiology of Microbial Diseases, Yale School of Public Health, 60 College Street, P.O. Box 208034, New Haven, CT, 06520-8034, USA; Department of Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, P.O. Box 208057, 300 Cedar Street TAC - 441 South, New Haven, CT, 06520-8057, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology of Microbial Diseases, Yale School of Public Health, 60 College Street, P.O. Box 208034, New Haven, CT, 06520-8034, USA; Department of Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, P.O. Box 208057, 300 Cedar Street TAC - 441 South, New Haven, CT, 06520-8057</wicri:regionArea></affiliation></author><author><name sortKey="Walter, Nicholas D" sort="Walter, Nicholas D" uniqKey="Walter N" first="Nicholas D" last="Walter">Nicholas D. Walter</name><affiliation wicri:level="1"><nlm:affiliation>Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Denver, Building 500 - 13001 E, 17th Place, Campus Box C290, Aurora, CO, 80045, USA; Pulmonary Section, Denver Veterans Affairs Medical Center, 1055 Clermont Street, Denver, CO, 80220, USA; Integrated Center for Genes, Environment, & Health, National Jewish Health, Smith Building; A647, 1400 Jackson Street, Denver, CO, 80206, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Denver, Building 500 - 13001 E, 17th Place, Campus Box C290, Aurora, CO, 80045, USA; Pulmonary Section, Denver Veterans Affairs Medical Center, 1055 Clermont Street, Denver, CO, 80220, USA; Integrated Center for Genes, Environment, & Health, National Jewish Health, Smith Building; A647, 1400 Jackson Street, Denver, CO, 80206</wicri:regionArea></affiliation></author><author><name sortKey="Garcia, Benjamin J" sort="Garcia, Benjamin J" uniqKey="Garcia B" first="Benjamin J" last="Garcia">Benjamin J. Garcia</name><affiliation wicri:level="1"><nlm:affiliation>Integrated Center for Genes, Environment, & Health, National Jewish Health, Smith Building; A647, 1400 Jackson Street, Denver, CO, 80206, USA; Computational Bioscience Program, University of Colorado Denver, Building 500 - 13001 E, 17th Place, Campus Box C290, Aurora, CO, 80045, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Integrated Center for Genes, Environment, & Health, National Jewish Health, Smith Building; A647, 1400 Jackson Street, Denver, CO, 80206, USA; Computational Bioscience Program, University of Colorado Denver, Building 500 - 13001 E, 17th Place, Campus Box C290, Aurora, CO, 80045</wicri:regionArea></affiliation></author><author><name sortKey="Voskuil, Marty" sort="Voskuil, Marty" uniqKey="Voskuil M" first="Marty" last="Voskuil">Marty Voskuil</name><affiliation wicri:level="1"><nlm:affiliation>Department of Immunology and Microbiology, University of Colorado School of Medicine, 12800 E. 19th Ave., Mail Stop 8333, Aurora, CO, 80045, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Immunology and Microbiology, University of Colorado School of Medicine, 12800 E. 19th Ave., Mail Stop 8333, Aurora, CO, 80045</wicri:regionArea></affiliation></author><author><name sortKey="Fissette, Kristina" sort="Fissette, Kristina" uniqKey="Fissette K" first="Kristina" last="Fissette">Kristina Fissette</name><affiliation wicri:level="1"><nlm:affiliation>Mycobacteriology Unit, Institute of Tropical Medicine (ITM), Nationalestraat 155, 2000, Antwerp, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Mycobacteriology Unit, Institute of Tropical Medicine (ITM), Nationalestraat 155, 2000, Antwerp</wicri:regionArea></affiliation></author><author><name sortKey="Diels, Maren" sort="Diels, Maren" uniqKey="Diels M" first="Maren" last="Diels">Maren Diels</name><affiliation wicri:level="1"><nlm:affiliation>Mycobacteriology Unit, Institute of Tropical Medicine (ITM), Nationalestraat 155, 2000, Antwerp, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Mycobacteriology Unit, Institute of Tropical Medicine (ITM), Nationalestraat 155, 2000, Antwerp</wicri:regionArea></affiliation></author><author><name sortKey="Driesen, Michele" sort="Driesen, Michele" uniqKey="Driesen M" first="Michèle" last="Driesen">Michèle Driesen</name><affiliation wicri:level="1"><nlm:affiliation>Mycobacteriology Unit, Institute of Tropical Medicine (ITM), Nationalestraat 155, 2000, Antwerp, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Mycobacteriology Unit, Institute of Tropical Medicine (ITM), Nationalestraat 155, 2000, Antwerp</wicri:regionArea></affiliation></author><author><name sortKey="Meehan, Conor J" sort="Meehan, Conor J" uniqKey="Meehan C" first="Conor J" last="Meehan">Conor J. Meehan</name><affiliation wicri:level="1"><nlm:affiliation>Mycobacteriology Unit, Institute of Tropical Medicine (ITM), Nationalestraat 155, 2000, Antwerp, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Mycobacteriology Unit, Institute of Tropical Medicine (ITM), Nationalestraat 155, 2000, Antwerp</wicri:regionArea></affiliation></author><author><name sortKey="Yeboah Manu, Dorothy" sort="Yeboah Manu, Dorothy" uniqKey="Yeboah Manu D" first="Dorothy" last="Yeboah-Manu">Dorothy Yeboah-Manu</name><affiliation wicri:level="1"><nlm:affiliation>Noguchi Memorial Institute for Medical Research, University of Ghana, P.O. Box LG 581, Legon, Accra, Ghana.</nlm:affiliation><country xml:lang="fr">Ghana</country><wicri:regionArea>Noguchi Memorial Institute for Medical Research, University of Ghana, P.O. Box LG 581, Legon, Accra</wicri:regionArea></affiliation></author><author><name sortKey="Coscolla, Mireia" sort="Coscolla, Mireia" uniqKey="Coscolla M" first="Mireia" last="Coscolla">Mireia Coscolla</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, P.O. Box 4002, Basel, Switzerland; University of Basel, Petersplatz 1, P.O. Box 4001, Basel, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, P.O. Box 4002, Basel, Switzerland; University of Basel, Petersplatz 1, P.O. Box 4001, Basel</wicri:regionArea></affiliation></author><author><name sortKey="Gagneux, Sebastien" sort="Gagneux, Sebastien" uniqKey="Gagneux S" first="Sebastien" last="Gagneux">Sebastien Gagneux</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, P.O. Box 4002, Basel, Switzerland; University of Basel, Petersplatz 1, P.O. Box 4001, Basel, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, P.O. Box 4002, Basel, Switzerland; University of Basel, Petersplatz 1, P.O. Box 4001, Basel</wicri:regionArea></affiliation></author><author><name sortKey="Antonio, Martin" sort="Antonio, Martin" uniqKey="Antonio M" first="Martin" last="Antonio">Martin Antonio</name><affiliation wicri:level="1"><nlm:affiliation>Vaccines and Immunity Theme, Medical Research Council (MRC) Unit, The Gambia, Atlantic Boulevard, Fajara, P.O. Box 273, Banjul, Gambia.</nlm:affiliation><country xml:lang="fr">Gambie</country><wicri:regionArea>Vaccines and Immunity Theme, Medical Research Council (MRC) Unit, The Gambia, Atlantic Boulevard, Fajara, P.O. Box 273, Banjul</wicri:regionArea></affiliation></author><author><name sortKey="Schoolnik, Gary" sort="Schoolnik, Gary" uniqKey="Schoolnik G" first="Gary" last="Schoolnik">Gary Schoolnik</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, Stanford University, 299 Campus Drive, Stanford, CA, 94305, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Stanford University, 299 Campus Drive, Stanford, CA, 94305</wicri:regionArea></affiliation></author><author><name sortKey="Gehre, Florian" sort="Gehre, Florian" uniqKey="Gehre F" first="Florian" last="Gehre">Florian Gehre</name><affiliation wicri:level="1"><nlm:affiliation>Mycobacteriology Unit, Institute of Tropical Medicine (ITM), Nationalestraat 155, 2000, Antwerp, Belgium; Vaccines and Immunity Theme, Medical Research Council (MRC) Unit, The Gambia, Atlantic Boulevard, Fajara, P.O. Box 273, Banjul, Gambia.</nlm:affiliation><country xml:lang="fr">Gambie</country><wicri:regionArea>Mycobacteriology Unit, Institute of Tropical Medicine (ITM), Nationalestraat 155, 2000, Antwerp, Belgium; Vaccines and Immunity Theme, Medical Research Council (MRC) Unit, The Gambia, Atlantic Boulevard, Fajara, P.O. Box 273, Banjul</wicri:regionArea></affiliation></author><author><name sortKey="De Jong, Bouke C" sort="De Jong, Bouke C" uniqKey="De Jong B" first="Bouke C" last="De Jong">Bouke C. De Jong</name><affiliation wicri:level="1"><nlm:affiliation>Mycobacteriology Unit, Institute of Tropical Medicine (ITM), Nationalestraat 155, 2000, Antwerp, Belgium. Electronic address: bdejong@itg.be.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Mycobacteriology Unit, Institute of Tropical Medicine (ITM), Nationalestraat 155, 2000, Antwerp</wicri:regionArea></affiliation></author></analytic><series><title level="j">Tuberculosis (Edinburgh, Scotland)</title><idno type="eISSN">1873-281X</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Mycobacterium africanum lineage (L) 6 is an important pathogen in West Africa, causing up to 40% of pulmonary tuberculosis (TB). The biology underlying the clinical differences between M. africanum and M. tuberculosis sensu stricto remains poorly understood. We performed ex vivo expression of 2179 genes of the most geographically dispersed cause of human TB, M. tuberculosis L4 and the geographically restricted, M. africanum L6 directly from sputa of 11 HIV-negative TB patients from The Gambia who had not started treatment. The DosR regulon was the most significantly decreased category in L6 relative to L4. Further, we identified nonsynonymous mutations in major DosR regulon genes of 44 L6 genomes of TB patients from The Gambia and Ghana. Using Lebek's test, we assessed differences in oxygen requirements for growth. L4 grew only at the aerobic surface while L6 grew throughout the medium. In the host, the DosR regulon is critical for M. tuberculosis in adaptation to oxygen limitation. However, M. africanum L6 appears to have adapted to growth under hypoxic conditions or to different biological niches. The observed under expression of DosR in L6 fits with the genomic changes in DosR genes, microaerobic growth and the association with extrapulmonary disease.</div></front></TEI><pubmed><MedlineCitation Status="In-Process" Owner="NLM"><PMID Version="1">28454650</PMID><DateCreated><Year>2017</Year><Month>04</Month><Day>29</Day></DateCreated><DateRevised><Year>2017</Year><Month>07</Month><Day>14</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1873-281X</ISSN><JournalIssue CitedMedium="Internet"><Volume>104</Volume><PubDate><Year>2017</Year><Month>May</Month></PubDate></JournalIssue><Title>Tuberculosis (Edinburgh, Scotland)</Title><ISOAbbreviation>Tuberculosis (Edinb)</ISOAbbreviation></Journal><ArticleTitle>Significant under expression of the DosR regulon in M. tuberculosis complex lineage 6 in sputum.</ArticleTitle><Pagination><MedlinePgn>58-64</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S1472-9792(16)30496-6</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.tube.2017.03.001</ELocationID><Abstract><AbstractText>Mycobacterium africanum lineage (L) 6 is an important pathogen in West Africa, causing up to 40% of pulmonary tuberculosis (TB). The biology underlying the clinical differences between M. africanum and M. tuberculosis sensu stricto remains poorly understood. We performed ex vivo expression of 2179 genes of the most geographically dispersed cause of human TB, M. tuberculosis L4 and the geographically restricted, M. africanum L6 directly from sputa of 11 HIV-negative TB patients from The Gambia who had not started treatment. The DosR regulon was the most significantly decreased category in L6 relative to L4. Further, we identified nonsynonymous mutations in major DosR regulon genes of 44 L6 genomes of TB patients from The Gambia and Ghana. Using Lebek's test, we assessed differences in oxygen requirements for growth. L4 grew only at the aerobic surface while L6 grew throughout the medium. In the host, the DosR regulon is critical for M. tuberculosis in adaptation to oxygen limitation. However, M. africanum L6 appears to have adapted to growth under hypoxic conditions or to different biological niches. The observed under expression of DosR in L6 fits with the genomic changes in DosR genes, microaerobic growth and the association with extrapulmonary disease.</AbstractText><CopyrightInformation>Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Ofori-Anyinam</LastName><ForeName>Boatema</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Mycobacteriology Unit, Institute of Tropical Medicine (ITM), Nationalestraat 155, 2000, Antwerp, Belgium; Vaccines and Immunity Theme, Medical Research Council (MRC) Unit, The Gambia, Atlantic Boulevard, Fajara, P.O. Box 273, Banjul, Gambia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dolganov</LastName><ForeName>Gregory</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, Stanford University, 299 Campus Drive, Stanford, CA, 94305, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Van</LastName><ForeName>Tran</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, Stanford University, 299 Campus Drive, Stanford, CA, 94305, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Davis</LastName><ForeName>J Lucian</ForeName><Initials>JL</Initials><AffiliationInfo><Affiliation>Department of Epidemiology of Microbial Diseases, Yale School of Public Health, 60 College Street, P.O. Box 208034, New Haven, CT, 06520-8034, USA; Department of Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, P.O. Box 208057, 300 Cedar Street TAC - 441 South, New Haven, CT, 06520-8057, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Walter</LastName><ForeName>Nicholas D</ForeName><Initials>ND</Initials><AffiliationInfo><Affiliation>Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Denver, Building 500 - 13001 E, 17th Place, Campus Box C290, Aurora, CO, 80045, USA; Pulmonary Section, Denver Veterans Affairs Medical Center, 1055 Clermont Street, Denver, CO, 80220, USA; Integrated Center for Genes, Environment, & Health, National Jewish Health, Smith Building; A647, 1400 Jackson Street, Denver, CO, 80206, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Garcia</LastName><ForeName>Benjamin J</ForeName><Initials>BJ</Initials><AffiliationInfo><Affiliation>Integrated Center for Genes, Environment, & Health, National Jewish Health, Smith Building; A647, 1400 Jackson Street, Denver, CO, 80206, USA; Computational Bioscience Program, University of Colorado Denver, Building 500 - 13001 E, 17th Place, Campus Box C290, Aurora, CO, 80045, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Voskuil</LastName><ForeName>Marty</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Immunology and Microbiology, University of Colorado School of Medicine, 12800 E. 19th Ave., Mail Stop 8333, Aurora, CO, 80045, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fissette</LastName><ForeName>Kristina</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Mycobacteriology Unit, Institute of Tropical Medicine (ITM), Nationalestraat 155, 2000, Antwerp, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Diels</LastName><ForeName>Maren</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Mycobacteriology Unit, Institute of Tropical Medicine (ITM), Nationalestraat 155, 2000, Antwerp, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Driesen</LastName><ForeName>Michèle</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Mycobacteriology Unit, Institute of Tropical Medicine (ITM), Nationalestraat 155, 2000, Antwerp, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Meehan</LastName><ForeName>Conor J</ForeName><Initials>CJ</Initials><AffiliationInfo><Affiliation>Mycobacteriology Unit, Institute of Tropical Medicine (ITM), Nationalestraat 155, 2000, Antwerp, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yeboah-Manu</LastName><ForeName>Dorothy</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Noguchi Memorial Institute for Medical Research, University of Ghana, P.O. Box LG 581, Legon, Accra, Ghana.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Coscolla</LastName><ForeName>Mireia</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, P.O. Box 4002, Basel, Switzerland; University of Basel, Petersplatz 1, P.O. Box 4001, Basel, Switzerland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gagneux</LastName><ForeName>Sebastien</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, P.O. Box 4002, Basel, Switzerland; University of Basel, Petersplatz 1, P.O. Box 4001, Basel, Switzerland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Antonio</LastName><ForeName>Martin</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Vaccines and Immunity Theme, Medical Research Council (MRC) Unit, The Gambia, Atlantic Boulevard, Fajara, P.O. Box 273, Banjul, Gambia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Schoolnik</LastName><ForeName>Gary</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, Stanford University, 299 Campus Drive, Stanford, CA, 94305, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gehre</LastName><ForeName>Florian</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Mycobacteriology Unit, Institute of Tropical Medicine (ITM), Nationalestraat 155, 2000, Antwerp, Belgium; Vaccines and Immunity Theme, Medical Research Council (MRC) Unit, The Gambia, Atlantic Boulevard, Fajara, P.O. Box 273, Banjul, Gambia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>de Jong</LastName><ForeName>Bouke C</ForeName><Initials>BC</Initials><AffiliationInfo><Affiliation>Mycobacteriology Unit, Institute of Tropical Medicine (ITM), Nationalestraat 155, 2000, Antwerp, Belgium. Electronic address: bdejong@itg.be.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 AI061505</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2017</Year><Month>03</Month><Day>04</Day></ArticleDate></Article><MedlineJournalInfo><Country>Scotland</Country><MedlineTA>Tuberculosis (Edinb)</MedlineTA><NlmUniqueID>100971555</NlmUniqueID><ISSNLinking>1472-9792</ISSNLinking></MedlineJournalInfo><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>Bull Soc Med Afr Noire Lang Fr. 1973;18(4):477-84</RefSource><PMID Version="1">4209097</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Clin Microbiol. 2000 Jan;38(1):152-7</RefSource><PMID 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MajorTopicYN="N">Hypoxia</Keyword><Keyword MajorTopicYN="N">Mycobacterium africanum</Keyword><Keyword MajorTopicYN="N">Mycobacterium tuberculosis</Keyword><Keyword MajorTopicYN="N">Sputum</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2016</Year><Month>11</Month><Day>18</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2017</Year><Month>02</Month><Day>21</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2017</Year><Month>03</Month><Day>02</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2017</Year><Month>4</Month><Day>30</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2017</Year><Month>4</Month><Day>30</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate 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