ArticleAntimicrobial agents and chemotherapy2016
Bioluminescent Reporters for Rapid Mechanism of Action Assessment in Tuberculosis Drug Discovery.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 54 citations in OpenAlex.
- Identification and Evaluation of Dibasic Piperidines as Cell Wall Inhibitors againstACS infectious diseases · 2026Article
- Identification and Evaluation of dibasic piperidines as novel cell wall inhibitors againstbioRxiv : the preprint server for biology · 2026Article
- Thienopyrimidine amide analogs target MmpL3 inAntimicrobial agents and chemotherapy · 2025Article
- Microbiological evidence for the trisubstituted benzimidazoles targeting MmpL3 inAntimicrobial agents and chemotherapy · 2025Article
- Common Biological Properties ofACS infectious diseases · 2025Article
- Fragment-Based Development of Small Molecule Inhibitors TargetingJournal of medicinal chemistry · 2025Article
- Identification of a Series Containing a Pentafluorophenyl Moiety That Targets Pks13 to Inhibit Growth ofACS infectious diseases · 2025Article
- Arenicolide Family Macrolides Provide a New Therapeutic Lead Combating Multidrug-Resistant Tuberculosis.Angewandte Chemie (International ed. in English) · 2025Article
- Developing novel indoles as antitubercular agents and simulated annealing-based analysis of their binding with MmpL3.Future medicinal chemistry · 2025Article
- An arylsulfonamide that targets cell wall biosynthesis inAntimicrobial agents and chemotherapy · 2024Article
- Synthesis and Structure-Activity Relationships of a New Class of Oxadiazoles Targeting DprE1 as Antitubercular Agents.ACS medicinal chemistry letters · 2023Article
- 1,3-Diarylpyrazolyl-acylsulfonamides Target HadAB/BC Complex inACS infectious diseases · 2022Article
- Spiropyrimidinetriones: a Class of DNA Gyrase Inhibitors with Activity against Mycobacterium tuberculosis and without Cross-Resistance to Fluoroquinolones.Antimicrobial agents and chemotherapy · 2022Article
- DNA-Dependent Binding of Nargenicin to DnaE1 Inhibits Replication inACS infectious diseases · 2022Article
- Synthetic approaches to potent heterocyclic inhibitors of tuberculosis: A decade review.Frontiers in pharmacology · 2022Review
- "Upcycling" known molecules and targets for drug-resistant TB.Frontiers in cellular and infection microbiology · 2022Article
- 1,3-Diarylpyrazolyl-acylsulfonamides as Potent Anti-tuberculosis Agents Targeting Cell Wall Biosynthesis inJournal of medicinal chemistry · 2021Article
- Piperidine-4-Carboxamides Target DNA Gyrase in Mycobacterium abscessus.Antimicrobial agents and chemotherapy · 2021Article
- Article
- The pursuit of mechanism of action: uncovering drug complexity in TB drug discovery.RSC chemical biology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The tuberculosis (TB) drug discovery pipeline is fueled by compounds identified in whole-cell screens against the causative agent, Mycobacterium tuberculosis Phenotypic screening enables the selection of molecules that inhibit essential cellular functions in live, intact bacilli grown under a chosen in vitro condition. However, deducing the mechanism of action (MOA), which is important to avoid promiscuous targets, often requires significant biological resources in a lengthy process that risks decoupling medicinal chemistry and biology efforts. Therefore, there is a need to develop methods enabling rapid MOA assessment of putative "actives" for triage decisions. Here, we describe a modified version of a bioluminescence reporter assay that allows nondestructive detection of compounds targeting either of two macromolecular processes in M. tuberculosis: cell wall biosynthesis or maintenance of DNA integrity. Coupling the luxCDABE operon from Photorhabdus luminescens to mycobacterial promoters driving expression of the iniBAC operon (PiniB-LUX) or the DNA damage-inducible genes, recA (PrecA-LUX) or radA (PradA-LUX), provided quantitative detection in real time of compounds triggering expression of any of these promoters over an extended 10- to 12-day incubation. Testing against known anti-TB agents confirmed the specificity of each reporter in registering the MOA of the applied antibiotic in M. tuberculosis, independent of bactericidal or bacteriostatic activity. Moreover, profiles obtained for experimental compounds indicated the potential to infer complex MOAs in which multiple cellular processes are disrupted. These results demonstrate the utility of the reporters for early triage of compounds based on the provisional MOA and suggest their application to investigate polypharmacology in known and experimental anti-TB agents.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.