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

M. africanum L6 is an important pathogen in West Africa, causing up to 40% of pulmonary TB. Previous epidemiological studies showed clinical differences between M. africanum L6 and M. tuberculosis sensu stricto, including relative attenuation of M. africanum L6, yet the biology underlying the clinical differences remains poorly understood. Using ex vivo sputum expression data, researchers from MRC Unit The Gambia collaboratively show for the first time directly in sputum samples from patients with Tuberculosis (TB) that the DosR regulon was significantly less expressed in Mycobacterium africanum lineage (L) 6 compared to M. tuberculosis L4. In the host, the DosR regulon is critical for adaptation of M. tuberculosis to oxygen limitation and is known to increase intracellular survival and virulence, with an impaired function associated with M. tuberculosis attenuation. These findings, published in Tuberculosis Journal of Elsevier, show a clinically relevant lineage, M. africanum L6, that has relatively weaker induction of the DosR regulon and appears to have adapted to growth under hypoxic conditions or different biological niches.The study was supported by the European Research Council. M. africanum L6 permits to study factors that have contributed to the virulence and success of the Mycobacterium tuberculosis complex, which could be exploited to target further attenuation. Such studies will also improve understanding of additional biologically relevant differences between M. tuberculosis and M. africanum. When asked to comment on the findings, Boatema Ofori-Anyinam, PhD student and first author of this study said “We are excited by our findings as they highlight the need to understand TB strain differences better. As we gain further insights, we will enhance our understanding of disease pathogenesis and develop better therapies and diagnostics”
0g8a5534

Boatema Ofori-Anyinam, PhD student

Read more about the findings at Elsevier Ltd on https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5421582/   Acknowledgements The authors thank patients and colleagues at MRCG for their contribution to the present analysis. Authors Boatema Ofori-Anyinam, Gregory Dolganov, Tran Van, J. Lucian Davis, Nicholas D. Walter, Benjamin J. Garcia, Marty Voskuil, Kristina Fissette, Maren Diels, Michèle Driesen, Conor J. Meehan, Dorothy Yeboah-Manu, Mireia Coscolla, Sebastien Gagneux, Martin Antonio, Gary Schoolnik, Florian Gehre and Bouke C. de Jong