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

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dc.contributor.authorOfori-Anyinam, B.
dc.contributor.authorDolganov, G.
dc.contributor.authorVan, T.
dc.contributor.authorDavis, J.L.
dc.contributor.authorWalter, N.D.
dc.contributor.authorGarcia, B.J.
dc.contributor.authorVoskuil, M.
dc.contributor.authorFissette, K.
dc.contributor.authorDiels, M.
dc.contributor.authorDriesen, M.
dc.contributor.authorMeehan, C.J.
dc.contributor.authorYeboah-Manu, D.
dc.contributor.authorCoscolla, M.
dc.contributor.authorGagneux, S.
dc.contributor.authorAntonio, M.
dc.contributor.authorSchoolnik, G.
dc.contributor.authorGehre, F.
dc.contributor.authorde Jong, B.C.
dc.date.accessioned2019-02-08T08:51:16Z
dc.date.available2019-02-08T08:51:16Z
dc.date.issued2017-05
dc.description.abstractMycobacterium 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. © 2017 The Authorsen_US
dc.identifier.otherdoi: 10.1016/j.tube.2017.03.001
dc.identifier.urihttp://ugspace.ug.edu.gh/handle/123456789/27351
dc.language.isoenen_US
dc.publisherTuberculosisen_US
dc.subjectDosRen_US
dc.subjectGene expressionen_US
dc.subjectHypoxiaen_US
dc.subjectMycobacterium africanumen_US
dc.subjectMycobacterium tuberculosisen_US
dc.subjectSputumen_US
dc.titleSignificant under expression of the DosR regulon in M. tuberculosis complex lineage 6 in sputumen_US
dc.typeArticleen_US

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