Project description:Bacteria commonly adapt to stresses by altering gene expression. To understand the response of M. tuberculosis (MTB) to bedaquiline, we performed transcriptomics over a time-course on MTB bacilli exposed to the drug.
Project description:Sirturo or Bedaquiline has been shown to inhibit the ATP synthase of Mycobacterium tuberculosis. We used microarrays to investigate compound-induced gene expression changes in general as well as effects on the transcription of the different ATP synthase genes and other metabolic pathways. Log phase Mycobacterium tuberculosis were cultivated in Middlebrook 7H9 broth and treated with 1 M-BM-5M Bedaquiline. We have extracted RNA from five different time-points after treatment: 0 min (T0), 30 min (T30), 60 min (T60), 180 min (T180) and 360 min (T360).
Project description:The ability of Mycobacterium tuberculosis (Mtb) to adopt heterogeneous physiological states, underlies it’s success in evading the immune system and tolerating antibiotic killing. Drug tolerant phenotypes are a major reason why the tuberculosis (TB) mortality rate is so high, with over 1.8 million deaths annually. To develop new TB therapeutics that better treat the infection (faster and more completely), a systems-level approach is needed to reveal the complexity of network-based adaptations of Mtb. Here, we report the transcriptional response of Mtb to the drug Bedaquiline. We performed transcriptomic sequencing (RNA-seq) on Mtb bacilli at 4, 24, 72 h following exposure to the drug.
Project description:Sirturo or Bedaquiline has been shown to inhibit the ATP synthase of Mycobacterium tuberculosis. We used microarrays to investigate compound-induced gene expression changes in general as well as effects on the transcription of the different ATP synthase genes and other metabolic pathways.
Project description:Transcriptional profiling of M. smegmatis mc2155 grown on Hartmans de Bont (HdB) supplemented with 0.2% glycerol and 0.05% Tween80 challenged with 2 μg/ml Bedaquiline and Dimethyl sulfoxide (DMSO)
Project description:Background: Infectious diseases are still a leading cause of death and, with the emergence of drug resistance, pose a great threat to human health. New drugs are thus continually being developed, without their effects on the immune system being studied in-depth. Here we aim to evaluate the impact of a recently release anti-TB drug, named bedaquiline (BDQ), on the response of human macrophages infected with Mycobacterium tuberculosis (MTB). Results: Here, we used MTB resistant to BDQ as a model of bacterial infection to examine the impact of BDQ on the human macrophage response. Gene expression profiling has revealed about 1,500 genes differentially expressed in MTB infected macrophages incubated with BDQ. The expression of 499 genes was upregulated and that of 996 downregulated upon treatment. The gene set up-regulated by BDQ was significantly enriched for genes involved in glucose/phospholipid metabolism, lysosome and autophagy. We found similar results with uninfected macrophages-treated with BDQ. Conclusions: Our results highlight the importance to study the interactions between antibiotics and host cells at the molecular level to better understand the consequences of antibiotic treatment during infection