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Significant under expression of the DosR regulon in M. tuberculosis complex lineage 6 in sputum.

Identifieur interne : 000021 ( Main/Exploration ); précédent : 000020; suivant : 000022

Significant 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 :

RBID : pubmed:28454650

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


Affiliations:


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Le document en format XML

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<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>
<wicri:noRegion>Antwerp</wicri:noRegion>
</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="4">
<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>
<placeName>
<settlement type="city">Accra</settlement>
<region nuts="2">Région du Grand Accra</region>
</placeName>
<orgName type="university">Université du Ghana</orgName>
</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>
<wicri:noRegion>Basel</wicri:noRegion>
</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>
<wicri:noRegion>Basel</wicri:noRegion>
</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>
<wicri:noRegion>Banjul</wicri:noRegion>
</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>
<wicri:noRegion>94305</wicri:noRegion>
</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>
<wicri:noRegion>Banjul</wicri:noRegion>
</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>
<wicri:noRegion>Antwerp</wicri:noRegion>
</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>
<affiliations>
<list>
<country>
<li>Belgique</li>
<li>Gambie</li>
<li>Ghana</li>
<li>Suisse</li>
<li>États-Unis</li>
</country>
<region>
<li>Région du Grand Accra</li>
</region>
<settlement>
<li>Accra</li>
</settlement>
<orgName>
<li>Université du Ghana</li>
</orgName>
</list>
<tree>
<country name="Gambie">
<noRegion>
<name sortKey="Ofori Anyinam, Boatema" sort="Ofori Anyinam, Boatema" uniqKey="Ofori Anyinam B" first="Boatema" last="Ofori-Anyinam">Boatema Ofori-Anyinam</name>
</noRegion>
<name sortKey="Antonio, Martin" sort="Antonio, Martin" uniqKey="Antonio M" first="Martin" last="Antonio">Martin Antonio</name>
<name sortKey="Gehre, Florian" sort="Gehre, Florian" uniqKey="Gehre F" first="Florian" last="Gehre">Florian Gehre</name>
</country>
<country name="États-Unis">
<noRegion>
<name sortKey="Dolganov, Gregory" sort="Dolganov, Gregory" uniqKey="Dolganov G" first="Gregory" last="Dolganov">Gregory Dolganov</name>
</noRegion>
<name sortKey="Davis, J Lucian" sort="Davis, J Lucian" uniqKey="Davis J" first="J Lucian" last="Davis">J Lucian Davis</name>
<name sortKey="Garcia, Benjamin J" sort="Garcia, Benjamin J" uniqKey="Garcia B" first="Benjamin J" last="Garcia">Benjamin J. Garcia</name>
<name sortKey="Schoolnik, Gary" sort="Schoolnik, Gary" uniqKey="Schoolnik G" first="Gary" last="Schoolnik">Gary Schoolnik</name>
<name sortKey="Van, Tran" sort="Van, Tran" uniqKey="Van T" first="Tran" last="Van">Tran Van</name>
<name sortKey="Voskuil, Marty" sort="Voskuil, Marty" uniqKey="Voskuil M" first="Marty" last="Voskuil">Marty Voskuil</name>
<name sortKey="Walter, Nicholas D" sort="Walter, Nicholas D" uniqKey="Walter N" first="Nicholas D" last="Walter">Nicholas D. Walter</name>
</country>
<country name="Belgique">
<noRegion>
<name sortKey="Fissette, Kristina" sort="Fissette, Kristina" uniqKey="Fissette K" first="Kristina" last="Fissette">Kristina Fissette</name>
</noRegion>
<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>
<name sortKey="Diels, Maren" sort="Diels, Maren" uniqKey="Diels M" first="Maren" last="Diels">Maren Diels</name>
<name sortKey="Driesen, Michele" sort="Driesen, Michele" uniqKey="Driesen M" first="Michèle" last="Driesen">Michèle Driesen</name>
<name sortKey="Meehan, Conor J" sort="Meehan, Conor J" uniqKey="Meehan C" first="Conor J" last="Meehan">Conor J. Meehan</name>
</country>
<country name="Ghana">
<region name="Région du Grand Accra">
<name sortKey="Yeboah Manu, Dorothy" sort="Yeboah Manu, Dorothy" uniqKey="Yeboah Manu D" first="Dorothy" last="Yeboah-Manu">Dorothy Yeboah-Manu</name>
</region>
</country>
<country name="Suisse">
<noRegion>
<name sortKey="Coscolla, Mireia" sort="Coscolla, Mireia" uniqKey="Coscolla M" first="Mireia" last="Coscolla">Mireia Coscolla</name>
</noRegion>
<name sortKey="Gagneux, Sebastien" sort="Gagneux, Sebastien" uniqKey="Gagneux S" first="Sebastien" last="Gagneux">Sebastien Gagneux</name>
</country>
</tree>
</affiliations>
</record>

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