Bedaquiline remodels the macrophage response

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 Evaluation of host response to BDQ treatment in infected and uninfected human macrophages.