ArticleNature communications2022
Anti-infective therapy using species-specific activators of Staphylococcus aureus ClpP.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 40 citations in OpenAlex.
- A secreted AIP-Like peptide fromVirulence · 2026Article
- Targeting ClpP Protease: Emerging Therapeutic Strategies and Small-Molecule Modulators in Drug Discovery.Medicinal research reviews · 2026Review
- Copper ions restore antibacterial activity of tigecycline by regulating photodegradation pathway under light exposure.Communications biology · 2026Article
- Polydatin as a natural ClpP modulator for combating methicillin-resistantFrontiers in cellular and infection microbiology · 2026Article
- Allosteric regulation of proteolytic machines unveiled by the synergy between cryo-EM and solution NMR spectroscopy.The Biochemical journal · 2025Review
- Mechanism of allosteric activation in human mitochondrial ClpP protease.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Structure-guided development of selective caseinolytic protease P agonists as antistaphylococcal agents.Cell reports. Medicine · 2024Article
- Identification of potential inhibitors againstJournal of enzyme inhibition and medicinal chemistry · 2024Article
- Protein degradation by a component of the chaperonin-linked protease ClpP.Genes to cells : devoted to molecular & cellular mechanisms · 2024Review
- Discovery of Potential Anti-Microbial Molecules and Spectrum Correlation Effect ofMolecules (Basel, Switzerland) · 2024Article
- Molecular insights into the dynamic modulation of bacterial ClpP function and oligomerization by peptidomimetic boronate compounds.Scientific reports · 2024Article
- Selective activator of human ClpP triggers cell cycle arrest to inhibit lung squamous cell carcinoma.Nature communications · 2023Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The emergence of methicillin-resistant Staphylococcus aureus isolates highlights the urgent need to develop more antibiotics. ClpP is a highly conserved protease regulated by ATPases in bacteria and in mitochondria. Aberrant activation of bacterial ClpP is an alternative method of discovering antibiotics, while it remains difficult to develop selective Staphylococcus aureus ClpP activators that can avoid disturbing Homo sapiens ClpP functions. Here, we use a structure-based design to identify (R)- and (S)-ZG197 as highly selective Staphylococcus aureus ClpP activators. The key structural elements in Homo sapiens ClpP, particularly W146 and its joint action with the C-terminal motif, significantly contribute to the discrimination of the activators. Our selective activators display wide antibiotic properties towards an array of multidrug-resistant staphylococcal strains in vitro, and demonstrate promising antibiotic efficacy in zebrafish and murine skin infection models. Our findings indicate that the species-specific activators of Staphylococcus aureus ClpP are exciting therapeutic agents to treat staphylococcal infections.
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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.