ArticlePLoS pathogens2016
Methylfolate Trap Promotes Bacterial Thymineless Death by Sulfa Drugs.
Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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.
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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
22 citing papers in PubMed, 39 citations in OpenAlex.
- Cobamide metabolism, regulation, and adaptation inJournal of bacteriology · 2025Review
- The T120P or M172V mutation onEmerging microbes & infections · 2024Article
- The gut microbiome regulates the clinical efficacy of sulfasalazine therapy for IBD-associated spondyloarthritis.Cell reports. Medicine · 2024Article
- Identification of a Potential Antimycobacterial Drug Sensitizer Targeting a Flavin-Independent Methylenetetrahydrofolate Reductase.ACS omega · 2023Article
- Methionyl-tRNA formyltransferase utilizes 10-formyldihydrofolate as an alternative substrate and impacts antifolate drug action.Microbiology (Reading, England) · 2023Article
- Thymine-starvation-induced chromosomal fragmentation is not required for thymineless death in Escherichia coli.Molecular microbiology · 2022Article
- Decreased Methylenetetrahydrofolate Reductase Activity Leads to Increased Sensitivity toAntimicrobial agents and chemotherapy · 2022Article
- Review
- Cobalamin is present in cells of non-tuberculous mycobacteria, but not in Mycobacterium tuberculosis.Scientific reports · 2021Article
- Surprising Homolytic Gas Phase Co-C Bond Dissociation Energies of Organometallic Aryl-Cobinamides Reveal Notable Non-Bonded Intramolecular Interactions.Chemistry (Weinheim an der Bergstrasse, Germany) · 2021Article
- The Pup-Proteasome System Protects Mycobacteria from Antimicrobial Antifolates.Antimicrobial agents and chemotherapy · 2021Article
- Article
- MgrB Inactivation Confers Trimethoprim Resistance inFrontiers in microbiology · 2021Article
- Antivitamins BChemistry (Weinheim an der Bergstrasse, Germany) · 2020Review
- Monomeric NADH-Oxidizing Methylenetetrahydrofolate Reductases from Mycobacterium smegmatis Lack Flavin Coenzyme.Journal of bacteriology · 2020Article
- Exceptional Photochemical Stability of the Co-C Bond of Alkynyl Cobalamins, Potential Antivitamins BInorganic chemistry · 2020Article
- Functional Disassociation Between the Protein Domains of MSMEG_4305 ofFrontiers in microbiology · 2020Article
- Thymineless Death inJournal of bacteriology · 2019Article
- Purifying Selective Pressure Suggests the Functionality of a Vitamin B12 Biosynthesis Pathway in a Global Population of Mycobacterium tuberculosis.Genome biology and evolution · 2018Article
- Deletion ofAntimicrobial agents and chemotherapy · 2017Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
Abstract
The methylfolate trap, a metabolic blockage associated with anemia, neural tube defects, Alzheimer's dementia, cardiovascular diseases, and cancer, was discovered in the 1960s, linking the metabolism of folate, vitamin B12, methionine and homocysteine. However, the existence or physiological significance of this phenomenon has been unknown in bacteria, which synthesize folate de novo. Here we identify the methylfolate trap as a novel determinant of the bacterial intrinsic death by sulfonamides, antibiotics that block de novo folate synthesis. Genetic mutagenesis, chemical complementation, and metabolomic profiling revealed trap-mediated metabolic imbalances, which induced thymineless death, a phenomenon in which rapidly growing cells succumb to thymine starvation. Restriction of B12 bioavailability, required for preventing trap formation, using an "antivitamin B12" molecule, sensitized intracellular bacteria to sulfonamides. Since boosting the bactericidal activity of sulfonamides through methylfolate trap induction can be achieved in Gram-negative bacteria and mycobacteria, it represents a novel strategy to render these pathogens more susceptible to existing sulfonamides.
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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.