Differential transcriptomic and metabolic profiles of M. africanum- and M. tuberculosis-infected patients after, but not before, drug treatment.


Tientcheu, LD; Maertzdorf, J; Weiner, J; Adetifa, IM; Mollenkopf, HJ; Sutherland, JS; Donkor, S; Kampmann, B; Kaufmann, SH; Dockrell, HM; Ota, MO; (2015) Differential transcriptomic and metabolic profiles of M. africanum- and M. tuberculosis-infected patients after, but not before, drug treatment. Genes and immunity, 16 (5). pp. 347-55. ISSN 1466-4879 DOI: 10.1038/gene.2015.21

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Abstract

: The epidemiology of Mycobacterium tuberculosis (Mtb) and M. africanum (Maf) suggests differences in their virulence, but the host immune profile to better understand the pathogenesis of tuberculosis (TB) have not been studied. We compared the transcriptomic and metabolic profiles between Mtb- and Maf-infected TB cases to identify host biomarkers associated with lineages-specific pathogenesis and response to anti-TB chemotherapy. Venous blood samples from Mtb- and Maf-infected patients obtained before and after anti-TB treatment were analyzed for cell composition, gene expression and metabolic profiles. Prior to treatment, similar transcriptomic profiles were seen in Maf- and Mtb-infected patients. In contrast, post treatment, over 1600 genes related to immune responses and metabolic diseases were differentially expressed between the groups. Notably, the upstream regulator hepatocyte nuclear factor 4-alpha (HNF4α), which regulated 15% of these genes, was markedly enriched. Serum metabolic profiles were similar in both group pre-treatment, but the decline in pro-inflammatory metabolites post treatment were most pronounced in Mtb-infected patients. Together, the differences in both peripheral blood transcriptomic and serum metabolic profiles between Maf- and Mtb-infected patients observed over the treatment period, might be indicative of intrinsic host factors related to susceptibility to TB and/or differential efficacy of the standard anti-TB treatment on the two lineages.<br/>

Item Type: Article
Faculty and Department: Academic Services & Administration > Academic Administration
Faculty of Epidemiology and Population Health > Dept of Population Health (2012- ) > Dept of Nutrition and Public Health Interventions Research (2003-2012)
Faculty of Epidemiology and Population Health > Dept of Population Health (2012- )
Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Research Centre: TB Centre
PubMed ID: 26043170
Web of Science ID: 358375500007
URI: http://researchonline.lshtm.ac.uk/id/eprint/2210725

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