ArticlePloS one2015
A high-throughput cidality screen for Mycobacterium tuberculosis.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Homo-BacPROTAC-induced degradation of ClpC1 as a strategy against drug-resistant mycobacteria.Nature communications · 2024Article
- A Novel Inhibitor against the Biofilms of Non-Tuberculous Mycobacteria.Pathogens (Basel, Switzerland) · 2023Article
- Antimicrobial Peptides as Immunomodulators and Antimycobacterial Agents to Combat Mycobacterium tuberculosis: a Critical Review.Probiotics and antimicrobial proteins · 2023Review
- Mannose-conjugated chitosan nanoparticles for delivery of Rifampicin to Osteoarticular tuberculosis.Drug delivery and translational research · 2021Article
- Inhibition of Biofilm Formation by the Synergistic Action of EGCG-S and Antibiotics.Antibiotics (Basel, Switzerland) · 2021Article
- Inhibition of biofilm formation in Mycobacterium smegmatis by Parinari curatellifolia leaf extracts.BMC complementary and alternative medicine · 2017Article
- Article
- Rapid, Semiquantitative Assay To Discriminate among Compounds with Activity against Replicating or Nonreplicating Mycobacterium tuberculosis.Antimicrobial agents and chemotherapy · 2015Article
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Exposure to Mycobacterium tuberculosis (Mtb) aerosols is a major threat to tuberculosis (TB) researchers, even in bio-safety level-3 (BSL-3) facilities. Automation and high-throughput screens (HTS) in BSL3 facilities are essential for minimizing manual aerosol-generating interventions and facilitating TB research. In the present study, we report the development and validation of a high-throughput, 24-well 'spot-assay' for selecting bactericidal compounds against Mtb. The bactericidal screen concept was first validated in the fast-growing surrogate Mycobacterium smegmatis (Msm) and subsequently confirmed in Mtb using the following reference anti-tubercular drugs: rifampicin, isoniazid, ofloxacin and ethambutol (RIOE, acting on different targets). The potential use of the spot-assay to select bactericidal compounds from a large library was confirmed by screening on Mtb, with parallel plating by the conventional gold standard method (correlation, r2 = 0.808). An automated spot-assay further enabled an MBC90 determination on resistant and sensitive Mtb clinical isolates. The implementation of the spot-assay in kinetic screens to enumerate residual Mtb after either genetic silencing (anti-sense RNA, AS-RNA) or chemical inhibition corroborated its ability to detect cidality. This relatively simple, economical and quantitative HTS considerably minimized the bio-hazard risk and enabled the selection of novel vulnerable Mtb targets and mycobactericidal compounds. Thus, spot-assays have great potential to impact the TB drug discovery process.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.