Ofori-Anyinam Boatema, Dolganov Gregory, Van Tran, Davis J Lucian, Walter Nicholas D, Garcia Benjamin J, Voskuil Marty, Fissette Kristina, Diels Maren, Driesen Michèle, Meehan Conor J, Yeboah-Manu Dorothy, Coscolla Mireia, Gagneux Sebastien, Antonio Martin, Schoolnik Gary, Gehre Florian, de Jong Bouke C
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.
Department of Microbiology and Immunology, Stanford University, 299 Campus Drive, Stanford, CA, 94305, USA.
Tuberculosis (Edinb). 2017 May;104:58-64. doi: 10.1016/j.tube.2017.03.001. Epub 2017 Mar 4.
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.
非洲分枝杆菌谱系（L）6是西非的一种重要病原体，导致高达40%的肺结核（TB）。非洲分枝杆菌与狭义结核分枝杆菌临床差异背后的生物学机制仍知之甚少。我们直接从11名来自冈比亚且尚未开始治疗的HIV阴性肺结核患者的痰液中，对人类结核病最具地理分布性的病原体——结核分枝杆菌L4和地理分布受限的非洲分枝杆菌L6的2179个基因进行了体外表达。相对于L4，DosR调控子是L6中最显著下调的类别。此外，我们在来自冈比亚和加纳的44例肺结核患者的L6基因组的主要DosR调控子基因中鉴定出非同义突变。使用莱贝克试验，我们评估了生长所需氧气的差异。L4仅在有氧表面生长，而L6在整个培养基中生长。在宿主体内，DosR调控子对于结核分枝杆菌适应氧气限制至关重要。然而，非洲分枝杆菌L6似乎已经适应了在低氧条件下生长或不同的生态位。在L6中观察到的DosR表达下调与DosR基因的基因组变化、微需氧生长以及与肺外疾病的关联相吻合。
