ArticleJournal of proteome research2014
Metabolomics analysis identifies d-Alanine-d-Alanine ligase as the primary lethal target of d-Cycloserine in mycobacteria.
Article in Journal of proteome research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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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Who cites it
35 citing papers in PubMed, 72 citations in OpenAlex.
- Cycloserine inhibits glutamate decarboxylase fromJournal of enzyme inhibition and medicinal chemistry · 2026Article
- The Pyridoxal-5'-Phosphate-Dependent Enzymes ofACS infectious diseases · 2026Review
- D-alanine synthesis and exogenous alanine affect the antimicrobial susceptibility ofAntimicrobial agents and chemotherapy · 2025Article
- Simulated LC-MS Data Set for Assessing the Metabolomics Data Processing Pipeline Implemented into MVAPACK.Analytical chemistry · 2024Article
- Dual transcriptional inhibition of glutamate and alanine racemase is synergistic inMicrobiology (Reading, England) · 2024Article
- Review
- Cytotoxic and Antiproliferative Activity of LASSBio-2208 and the Attempts to Determine Its Drug Metabolism and Pharmacokinetics In Vitro Profile.Pharmaceuticals (Basel, Switzerland) · 2024Article
- How do Mutations of Mycobacterium Genes Cause Drug Resistance in Tuberculosis?Current pharmaceutical biotechnology · 2024Review
- Wollamide Cyclic Hexapeptides Synergize with Established and New Tuberculosis Antibiotics in Targeting Mycobacterium tuberculosis.Microbiology spectrum · 2023Article
- Deciphering the mechanism of action of antitubercular compounds with metabolomics.Computational and structural biotechnology journal · 2021Review
- Antibiotics and resistance: the two-sided coin of the mycobacterial cell wall.Cell surface (Amsterdam, Netherlands) · 2020Review
- Integron gene cassettes harboring novel variants of D-alanine-D-alanine ligase confer high-level resistance to D-cycloserine.Scientific reports · 2020Article
- Inhibition ofAntibiotics (Basel, Switzerland) · 2020Article
- c-di-AMP Accumulation Impairs Muropeptide Synthesis in Listeria monocytogenes.Journal of bacteriology · 2020Article
- Mycobacterium tuberculosis curli pili (MTP) deficiency is associated with alterations in cell wall biogenesis, fatty acid metabolism and amino acid synthesis.Metabolomics : Official journal of the Metabolomic Society · 2020Article
- Genome Subtraction and Comparison for the Identification of Novel Drug Targets againstPathogens (Basel, Switzerland) · 2020Article
- DdlR, an essential transcriptional regulator of peptidoglycan biosynthesis in Clostridioides difficile.Molecular microbiology · 2019Article
- Deficiency of D-alanyl-D-alanine ligase A attenuated cell division and greatly altered the proteome of Mycobacterium smegmatis.MicrobiologyOpen · 2019Article
- Metabolic interventions for the prevention and treatment of daptomycin non-susceptibility in Staphylococcus aureus.The Journal of antimicrobial chemotherapy · 2019Article
- Digging Deeper to Save the Old Anti-tuberculosis Target: D-Alanine-D-Alanine Ligase With a Novel Inhibitor, IMB-0283.Frontiers in microbiology · 2019Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
d-Cycloserine is an effective second line antibiotic used as a last resort to treat multi (MDR)- and extensively (XDR) drug resistant strains of Mycobacterium tuberculosis . d-Cycloserine interferes with the formation of peptidoglycan biosynthesis by competitive inhibition of alanine racemase (Alr) and d-alanine-d-alanine ligase (Ddl). Although the two enzymes are known to be inhibited, the in vivo lethal target is still unknown. Our NMR metabolomics work has revealed that Ddl is the primary target of DCS, as cell growth is inhibited when the production of d-alanyl-d-alanine is halted. It is shown that inhibition of Alr may contribute indirectly by lowering the levels of d-alanine, thus allowing DCS to outcompete d-alanine for Ddl binding. The NMR data also supports the possibility of a transamination reaction to produce d-alanine from pyruvate and glutamate, thereby bypassing Alr inhibition. Furthermore, the inhibition of peptidoglycan synthesis results in a cascading effect on cellular metabolism as there is a shift toward the catabolic routes to compensate for accumulation of peptidoglycan precursors.
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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.