ArticleScience (New York, N.Y.)2013
Para-aminosalicylic acid acts as an alternative substrate of folate metabolism in Mycobacterium tuberculosis.
Article in Science (New York, N.Y.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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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.
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Who cites it
105 citing papers in PubMed, 190 citations in OpenAlex.
- Mutations inJAC-antimicrobial resistance · 2026Article
- Identification of chemical features for improved outer membrane permeation in mycobacteria using machine learning.Nature microbiology · 2026Article
- MEP Pathway: First-Synthesized IspH-Directed Prodrugs with Potent Antimycobacterial Activity.Microorganisms · 2026Article
- A Comprehensive Review of Genetic Mechanisms ofInfection and drug resistance · 2026Review
- Development of Pyrimido Pyridazine Analogs through Increased Whole Cell Target Engagement of the Dihydropteroate Synthase Pterin Binding Site in Gram-Negative Bacteria.ACS infectious diseases · 2025Article
- Trehalose catalytic shift inherently enhances phenotypic heterogeneity and multidrug resistance in Mycobacterium tuberculosis.Nature communications · 2025Article
- Identification of chemical features that influence mycomembrane permeation and antitubercular activity.bioRxiv : the preprint server for biology · 2025Article
- The T120P or M172V mutation onEmerging microbes & infections · 2024Article
- Integrating bacterial molecular genetics with chemical biology for renewed antibacterial drug discovery.The Biochemical journal · 2024Review
- Antitubercular drugs: possible role of natural products acting as antituberculosis medication in overcoming drug resistance and drug-induced hepatotoxicity.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Article
- The aminosalicylate - folate connection.Drug metabolism reviews · 2024Review
- Spermine enhances the activity of anti-tuberculosis drugs.Microbiology spectrum · 2024Article
- Pyrazinoic acid, the active form of the anti-tuberculosis drug pyrazinamide, and aromatic carboxylic acid analogs are protonophores.Frontiers in molecular biosciences · 2024Article
- Competition between HAntibiotics (Basel, Switzerland) · 2023Article
- New nitazoxanide derivatives: design, synthesis, biological evaluation, and molecular docking studies as antibacterial and antimycobacterial agents.RSC medicinal chemistry · 2023Article
- Whole genome sequencing reveals candidate genes involving in PAS resistance in M. Tuberculosis isolated from patients in Thailand.World journal of microbiology & biotechnology · 2023Article
- Association between mutations in aEmerging microbes & infections · 2023Article
- Characterization of Graft Copolymers Synthesized fromPharmaceutics · 2023Article
- Review
45 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Folate biosynthesis is an established anti-infective target, and the antifolate para-aminosalicylic acid (PAS) was one of the first anti-infectives introduced into clinical practice on the basis of target-based drug discovery. Fifty years later, PAS continues to be used to treat tuberculosis. PAS is assumed to inhibit dihydropteroate synthase (DHPS) in Mycobacterium tuberculosis by mimicking the substrate p-aminobenzoate (PABA). However, we found that sulfonamide inhibitors of DHPS inhibited growth of M. tuberculosis only weakly because of their intracellular metabolism. In contrast, PAS served as a replacement substrate for DHPS. Products of PAS metabolism at this and subsequent steps in folate metabolism inhibited those enzymes, competing with their substrates. PAS is thus a prodrug that blocks growth of M. tuberculosis when its active forms are generated by enzymes in the pathway they poison.
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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.