ArticleScientific reports2018
Antimycobacterial drug discovery using Mycobacteria-infected amoebae identifies anti-infectives and new molecular targets.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
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- Reference-based chemical-genetic interaction profiling to elucidate small molecule mechanism of action in Mycobacterium tuberculosis.Nature communications · 2025Article
- SMURF2 inhibits autophagic control ofbioRxiv : the preprint server for biology · 2025Article
- Article
- Temporal genome-wide fitness analysis ofmSystems · 2024Article
- Discovery of anti-infective compounds againstFrontiers in microbiology · 2024Article
- Molecular Mechanisms of MmpL3 Function and Inhibition.Microbial drug resistance (Larchmont, N.Y.) · 2023Review
- High-Throughput Screen for Inhibitors ofACS omega · 2022Article
- Cryo-EM structure and resistance landscape of M. tuberculosis MmpL3: An emergent therapeutic target.Structure (London, England : 1993) · 2021Article
- Structural and Functional Diversity of Resistance-Nodulation-Cell Division Transporters.Chemical reviews · 2021Review
- Two-Way Regulation of MmpL3 Expression Identifies and Validates Inhibitors of MmpL3 Function inACS infectious diseases · 2021Article
- Preclinical Models of Nontuberculous Mycobacteria Infection for Early Drug Discovery and Vaccine Research.Pathogens (Basel, Switzerland) · 2020Review
- Identification of Anti-Frontiers in microbiology · 2020Article
- Editorial: Amoebae as Host Models to Study the Interaction With Pathogens.Frontiers in cellular and infection microbiology · 2019Article
- A New Single Gene Differential Biomarker forFrontiers in microbiology · 2019Article
- A reevaluation of iron binding by Mycobactin J.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2018Article
- Identification of Virulence Markers of Mycobacterium abscessus for Intracellular Replication in Phagocytes.Journal of visualized experiments : JoVE · 2018Article
- When Dicty Met Myco, a (Not So) Romantic Story about One Amoeba and Its Intracellular Pathogen.Frontiers in cellular and infection microbiology · 2017Review
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Authors and funding
12 authors.
Funding
Abstract
Tuberculosis remains a serious threat to human health world-wide, and improved efficiency of medical treatment requires a better understanding of the pathogenesis and the discovery of new drugs. In the present study, we performed a whole-cell based screen in order to complete the characterization of 168 compounds from the GlaxoSmithKline TB-set. We have established and utilized novel previously unexplored host-model systems to characterize the GSK compounds, i.e. the amoeboid organisms D. discoideum and A. castellanii, as well as a microglial phagocytic cell line, BV2. We infected these host cells with Mycobacterium marinum to monitor and characterize the anti-infective activity of the compounds with quantitative fluorescence measurements and high-content microscopy. In summary, 88.1% of the compounds were confirmed as antibiotics against M. marinum, 11.3% and 4.8% displayed strong anti-infective activity in, respectively, the mammalian and protozoan infection models. Additionally, in the two systems, 13-14% of the compounds displayed pro-infective activity. Our studies underline the relevance of using evolutionarily distant pathogen and host models in order to reveal conserved mechanisms of virulence and defence, respectively, which are potential "universal" targets for intervention. Subsequent mechanism of action studies based on generation of over-expresser M. bovis BCG strains, generation of spontaneous resistant mutants and whole genome sequencing revealed four new molecular targets, including FbpA, MurC, MmpL3 and GlpK.
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