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dc.date.accessioned2020-01-16T12:29:43Z
dc.date.available2020-01-16T12:29:43Z
dc.date.issued2017-05
dc.identifier.citationOfori-Anyinam B, Dolganov G, Van T et al (2017) Significant under expression of the DosR regulon in M. tuberculosis complex lineage 6 in sputum. Tuberculosis. 104: 58-64.
dc.identifier.urihttp://hdl.handle.net/10454/17574
dc.descriptionYes
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.
dc.description.sponsorshipEuropean Research Council-INTERRUPTB starting grant nr.311725 (to BdJ, BO, FG, MA, CM).
dc.language.isoen
dc.rights© 2017 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
dc.subjectMycobacterium africanum
dc.subjectMycobacterium tuberculosis
dc.subjectHypoxia
dc.subjectSputum
dc.subjectGene expression
dc.subjectDosR
dc.titleSignificant under expression of the DosR regulon in M. tuberculosis complex lineage 6 in sputum
dc.status.refereedYes
dc.date.Accepted2017-03-02
dc.date.application2017-03-04
dc.typeArticle
dc.type.versionPublished version
dc.identifier.doihttps://doi.org/10.1016/j.tube.2017.03.001
dc.rights.licenseCC-BY-NC-ND
refterms.dateFOA2020-01-16T12:29:43Z
dc.openaccess.statusopenAccess


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