ArticleAntimicrobial agents and chemotherapy2015
The cyclic peptide ecumicin targeting ClpC1 is active against Mycobacterium tuberculosis in vivo.
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 96 papers.
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96 citing papers in PubMed.
- Small-molecule activators of theiScience · 2026Article
- Microbial Natural Products Targeting theMicroorganisms · 2026Review
- Pushing the limits of single-cell proteomics to investigate bacterial heterogeneity using bacSCP.Nature communications · 2026Article
- ClpC1-dependent iron homeostasis underlies mycobacterial defense against oxygen-driven Fenton reaction during reactivation.Microbiology spectrum · 2026Article
- Phosphoarginine modulates oligomerization and repressor activity of mycobacterial ClpC2.bioRxiv : the preprint server for biology · 2026Article
- Review
- Proteostasis-targeted antibacterial strategies.Journal of microbiology (Seoul, Korea) · 2026Review
- ClpC1-targeting peptide natural products differentially dysregulate the proteome of Mycobacterium tuberculosis.Nature communications · 2026Article
- Article
- Antimycobacterial peptides as natural therapeutics for tuberculosis: mechanisms and structural features.Frontiers in antibiotics · 2026Review
- [Fe(phen)ACS omega · 2025Article
- Allosteric control of the bacterial ClpC/ClpP protease and its hijacking by antibacterial peptides.The EMBO journal · 2025Article
- Mutations in ClpC1 or ClpX subunit of caseinolytic protease confer resistance to ilamycins in mycobacteria.Communications biology · 2025Article
- Harnessing Actinobacteria secondary metabolites for tuberculosis drug discovery: Historical trends, current status and future outlooks.Natural products and bioprospecting · 2025Review
- The Identification of Novel Mutations in ATP-Dependent Protease ClpC1 Assists in the Molecular Diagnosis of Obscured Pyrazinamide-Resistant Tuberculosis Clinical Isolates.Microorganisms · 2025Article
- MdfA is a novel ClpC adaptor protein that functions in the developingGenes & development · 2025Article
- Evolution of Small Molecule Inhibitors ofJournal of medicinal chemistry · 2025Article
- Fighting Antimicrobial Resistance: Innovative Drugs in Antibacterial Research.Angewandte Chemie (International ed. in English) · 2025Review
- Identification of new ClpC1-NTD binders for Mycobacterium tuberculosis drug development.Scientific reports · 2025Article
- The effects of cyclic peptide [R4W4] in combination with first-line therapy on the survival ofFrontiers in cellular and infection microbiology · 2025Article
36 more citing papers are in PubMed but not listed here.
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21 authors.
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Abstract
Drug-resistant tuberculosis (TB) has lent urgency to finding new drug leads with novel modes of action. A high-throughput screening campaign of >65,000 actinomycete extracts for inhibition of Mycobacterium tuberculosis viability identified ecumicin, a macrocyclic tridecapeptide that exerts potent, selective bactericidal activity against M. tuberculosis in vitro, including nonreplicating cells. Ecumicin retains activity against isolated multiple-drug-resistant (MDR) and extensively drug-resistant (XDR) strains of M. tuberculosis. The subcutaneous administration to mice of ecumicin in a micellar formulation at 20 mg/kg body weight resulted in plasma and lung exposures exceeding the MIC. Complete inhibition of M. tuberculosis growth in the lungs of mice was achieved following 12 doses at 20 or 32 mg/kg. Genome mining of lab-generated, spontaneous ecumicin-resistant M. tuberculosis strains identified the ClpC1 ATPase complex as the putative target, and this was confirmed by a drug affinity response test. ClpC1 functions in protein breakdown with the ClpP1P2 protease complex. Ecumicin markedly enhanced the ATPase activity of wild-type (WT) ClpC1 but prevented activation of proteolysis by ClpC1. Less stimulation was observed with ClpC1 from ecumicin-resistant mutants. Thus, ClpC1 is a valid drug target against M. tuberculosis, and ecumicin may serve as a lead compound for anti-TB drug development.
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