ArticleAntimicrobial agents and chemotherapy2015
Rapid, Semiquantitative Assay To Discriminate among Compounds with Activity against Replicating or Nonreplicating Mycobacterium tuberculosis.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- Growth arrest of Mycobacterium tuberculosis in acidic environments enhances their survival of antibiotic treatment.PLoS biology · 2026Article
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- Bedaquiline Resistance: A Looming Global Threat in Tuberculosis Management.Current microbiology · 2025Review
- Increased proportion of growth-arrested bacilli in acidic pH adaptation promotesbioRxiv : the preprint server for biology · 2025Article
- Article
- Article
- SigH stress response mediates killing of Mycobacterium tuberculosis by activating nitronaphthofuran prodrugs via induction of Mrx2 expression.Nucleic acids research · 2023Article
- Advances in the design of combination therapies for the treatment of tuberculosis.Expert opinion on drug discovery · 2023Review
- In silico and in vitro study of Mycobacterium tuberculosis H37Rv uncharacterized protein (RipD): an insight on tuberculosis therapeutics.Journal of molecular modeling · 2022Article
- Spiropyrimidinetriones: a Class of DNA Gyrase Inhibitors with Activity against Mycobacterium tuberculosis and without Cross-Resistance to Fluoroquinolones.Antimicrobial agents and chemotherapy · 2022Article
- Identification of β-Lactams Active againstACS infectious diseases · 2022Article
- Tools to develop antibiotic combinations that target drug tolerance inFrontiers in cellular and infection microbiology · 2022Review
- Oxidative damage and delayed replication allow viableScience translational medicine · 2021Article
- Multiform antimicrobial resistance from a metabolic mutation.Science advances · 2021Article
- A Multistress Model for High Throughput Screening Against Nonreplicating Mycobacterium tuberculosis.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Determining Minimum Inhibitory Concentrations in Liquid Cultures or on Solid Medium.Methods in molecular biology (Clifton, N.J.) · 2021Article
- The quest for the holy grail: new antitubercular chemical entities, targets and strategies.Drug discovery today · 2020Review
- Article
- Activity-Based Protein Profiling Reveals That Cephalosporins Selectively Active on Non-replicatingFrontiers in microbiology · 2020Article
- Dual-Pharmacophore Pyrithione-Containing Cephalosporins Kill Both Replicating and NonreplicatingACS infectious diseases · 2019Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
The search for drugs that can kill replicating and nonreplicating Mycobacterium tuberculosis faces practical bottlenecks. Measurement of CFU and discrimination of bacteriostatic from bactericidal activity are costly in compounds, supplies, labor, and time. Testing compounds against M. tuberculosis under conditions that prevent the replication of M. tuberculosis often involves a second phase of the test in which conditions are altered to permit the replication of bacteria that survived the first phase. False-positive determinations of activity against nonreplicating M. tuberculosis may arise from carryover of compounds from the nonreplicating stage of the assay that act in the replicating stage. We mitigate these problems by carrying out a 96-well microplate liquid MIC assay and then transferring an aliquot of each well to a second set of plates in which each well contains agar supplemented with activated charcoal. After 7 to 10 days-about 2 weeks sooner than required to count CFU-fluorometry reveals whether M. tuberculosis bacilli in each well have replicated extensively enough to reduce a resazurin dye added for the final hour. This charcoal agar resazurin assay (CARA) distinguishes between bacterial biomasses in any two wells that differ by 2 to 3 log10 CFU. The CARA thus serves as a pretest and semiquantitative surrogate for longer, more laborious, and expensive CFU-based assays, helps distinguish bactericidal from bacteriostatic activity, and identifies compounds that are active under replicating conditions, nonreplicating conditions, or both. Results for 14 antimycobacterial compounds, including tuberculosis (TB) drugs, revealed that PA-824 (pretomanid) and TMC207 (bedaquiline) are largely bacteriostatic.
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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.