Scientific Service Bacterial Diseases - Infectious Diseases in Humans, Sciensano, Juliette Wytsmanstraat 14, 1050 Brussels, Belgium; National Reference Center of Mycobacteria and Tuberculosis - Infectious Diseases in Humans, Sciensano, Juliette Wytsmanstraat 14, 1050 Brussels, Belgium.
Institut Pasteur - Transcriptome and Epigenome Platform - Biomics Pole - C2RT, 28 Rue du Docteur Roux, 75015 Paris, France; Institut Pasteur - Bioinformatics and Biostatistics Hub - C3BI, USR 3756 IP CNRS, 28 Rue du Docteur Roux, 75015 Paris, France.
Tuberculosis (Edinb). 2019 Jul;117:18-23. doi: 10.1016/j.tube.2019.05.002. Epub 2019 May 15.
Tuberculosis (TB) is the most deadly infectious disease worldwide. To reduce TB incidence and counter the spread of multidrug resistant TB, the discovery and characterization of new drugs is essential. In this study, the transcriptional response of two Mycobacterium tuberculosis strains to a pressure of the recently approved delamanid is investigated. Total RNA sequencing revealed that the response to this bicyclic nitroimidazole shows many similarities with pretomanid, an anti-tuberculous drug from the same class. Although delamanid is found to inhibit cell wall synthesis, the expression of genes involved in this process were only mildly affected. In contrast, a clear parallel was found with components that affect aerobic respiration. This demonstrates that, besides the inhibition of cell wall synthesis, respiratory poisoning plays a fundamental role in the bactericidal effect of delamanid. Remarkably, the most highly induced genes comprise poorly characterized genes for which functional characterization might hint to the target molecule(s) of delamanid and its exact mode(s) of action.
结核病（TB）是全球最致命的传染病。为了降低结核病的发病率并遏制耐多药结核病的传播，发现和鉴定新的药物至关重要。在这项研究中，研究人员调查了两种结核分枝杆菌菌株对最近批准的德拉马尼的压力的转录反应。全转录组测序显示，这种双环硝基咪唑对这种双环硝基咪唑的反应与同类抗结核药物普托马尼有许多相似之处。尽管德拉马尼被发现抑制细胞壁合成，但参与这一过程的基因的表达仅受到轻微影响。相比之下，与影响有氧呼吸的成分明显平行。这表明，除了抑制细胞壁合成外，呼吸中毒在德拉马尼的杀菌作用中起着根本性的作用。值得注意的是，诱导表达最强的基因包括功能特征描述较差的基因，对这些基因的功能特征描述可能提示德拉马尼及其确切作用模式的靶分子（s）。
