ArticlePloS one2013
Identification of new drug targets and resistance mechanisms in Mycobacterium tuberculosis.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers.
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Who cites it
128 citing papers in PubMed, 250 citations in OpenAlex.
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- Integrating chemical, genetic, and feasibility assessments for anti-tubercular target validation.EMBO molecular medicine · 2026Review
- In-silico screening of marine fungal metabolites identifies potential FtsZ inhibitors against MDR-tuberculosis through docking and molecular dynamics analysis.Scientific reports · 2026Article
- MmpS5-MmpL5 Transporters DeliverCurrent protein & peptide science · 2026Article
- Uncovering Insights Into the Biology of Mycobacterium tuberculosis Using Genetic Tools.MicrobiologyOpen · 2025Review
- Thienopyrimidine amide analogs target MmpL3 inAntimicrobial agents and chemotherapy · 2025Article
- Reference-based chemical-genetic interaction profiling to elucidate small molecule mechanism of action in Mycobacterium tuberculosis.Nature communications · 2025Article
- Mutations in the Esx-3 secretion system confer resistance to multiple chemical scaffolds inMicrobiology (Reading, England) · 2025Article
- Scaffold Hopping in Tuberculosis Drug Discovery: Principles, Applications, and Case Studies.Journal of medicinal chemistry · 2025Review
- Identifying Modulators of the Post-Antibiotic Effect.ACS infectious diseases · 2025Article
- Discovery of 2,4,5-Substituted Benzoxazole Derivatives as Pks13 Inhibitors via the Scaffold Hopping Strategy.ACS infectious diseases · 2025Article
- Chemical genetic interactions elucidate pathways controlling tuberculosis antibiotic efficacy during infection.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- TheMicrobiology spectrum · 2024Article
- Polyketide Synthase 13 (Pks13) Inhibition: A Potential Target for New Class of Anti-tubercular Agents.Current topics in medicinal chemistry · 2024Review
- Identification and Optimization of Novel Inhibitors of the Polyketide Synthase 13 Thioesterase Domain with Antitubercular Activity.Journal of medicinal chemistry · 2023Article
- Screening and molecular dynamics simulation of compounds inhibiting MurB enzyme of drug-resistantSaudi journal of biological sciences · 2023Article
- Phase variation as a major mechanism of adaptation inProceedings of the National Academy of Sciences of the United States of America · 2023Article
- High-Throughput Screening of Natural Product and Synthetic Molecule Libraries for Antibacterial Drug Discovery.Metabolites · 2023Review
- Deletion of Rv2571c confers resistance to arylamide compounds inAntimicrobial agents and chemotherapy · 2023Article
- Therapeutic potential of coumestan Pks13 inhibitors for tuberculosis.Antimicrobial agents and chemotherapy · 2023Article
68 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 2 countries.
Funding
Abstract
Identification of new drug targets is vital for the advancement of drug discovery against Mycobacterium tuberculosis, especially given the increase of resistance worldwide to first- and second-line drugs. Because traditional target-based screening has largely proven unsuccessful for antibiotic discovery, we have developed a scalable platform for target identification in M. tuberculosis that is based on whole-cell screening, coupled with whole-genome sequencing of resistant mutants and recombineering to confirm. The method yields targets paired with whole-cell active compounds, which can serve as novel scaffolds for drug development, molecular tools for validation, and/or as ligands for co-crystallization. It may also reveal other information about mechanisms of action, such as activation or efflux. Using this method, we identified resistance-linked genes for eight compounds with anti-tubercular activity. Four of the genes have previously been shown to be essential: AspS, aspartyl-tRNA synthetase, Pks13, a polyketide synthase involved in mycolic acid biosynthesis, MmpL3, a membrane transporter, and EccB3, a component of the ESX-3 type VII secretion system. AspS and Pks13 represent novel targets in protein translation and cell-wall biosynthesis. Both MmpL3 and EccB3 are involved in membrane transport. Pks13, AspS, and EccB3 represent novel candidates not targeted by existing TB drugs, and the availability of whole-cell active inhibitors greatly increases their potential for drug discovery.
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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.