ArticlePloS one2016
A Conformationally Constrained Cyclic Acyldepsipeptide Is Highly Effective in Mice Infected with Methicillin-Susceptible and -Resistant Staphylococcus aureus.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 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.
The trial behind it
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
9 citing papers in PubMed.
- Natural products influence bacteriophage infectivity.Natural product reports · 2025Review
- Protein degradation by a component of the chaperonin-linked protease ClpP.Genes to cells : devoted to molecular & cellular mechanisms · 2024Review
- Prospects for Antibacterial Discovery and Development.Journal of the American Chemical Society · 2021Article
- Reprogramming of the Caseinolytic Protease by ADEP Antibiotics: Molecular Mechanism, Cellular Consequences, Therapeutic Potential.Frontiers in molecular biosciences · 2021Review
- Synthesis and Antichlamydial Activity of Molecules Based on Dysregulators of Cylindrical Proteases.Journal of medicinal chemistry · 2020Article
- Ureadepsipeptides as ClpP Activators.ACS infectious diseases · 2019Article
- Strategies against methicillin-resistant Staphylococcus aureus persisters.Future medicinal chemistry · 2018Review
- Whole-Genome-Sequencing characterization of bloodstream infection-causing hypervirulent Klebsiella pneumoniae of capsular serotype K2 and ST374.Virulence · 2018Article
- Bacterial proteases, untapped antimicrobial drug targets.The Journal of antibiotics · 2017Review
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
backgroundCyclic acyldepsipeptides (ADEPs) are a novel class of antibacterial agents, some of which (e.g., ADEP 4) are highly active against Gram-positive bacteria. The focus of these in vivo studies is ADEP B315, a rationally designed compound that has the most potent in vitro activity of any ADEP analog reported to date.
methodsIn vivo efficacy experiments were performed using lethal intraperitoneal mice infection models with a methicillin-sensitive S. aureus (MSSA) and a methicillin-resistant (MRSA) strain. The infected mice were treated with ADEP B315, a des-methyl analog of ADEP 4, vancomycin, or the vehicle used for the ADEPs and their survival was assessed daily. A subset of MSSA-infected mice was sacrificed soon after inoculation and the bacterial burden was measured in their livers and spleens. The toxicity of ADEP B315 was assessed in viability assays using human whole blood cultures.
resultsIn the MSSA experiments, all mice treated with the vehicle succumbed to the infection within 24 hours. All tested compounds were effective in prolonging survival of infected mice (p<0.001). Mice treated with ADEP B315 had a 39% survival rate by 10 days compared to 7% survival in mice treated with a des-methyl ADEP 4 analog (p = 0.017). Survival of the infected mice treated with ADEP B315 was comparable to those treated with vanocmycin (p = 0.12) at the same dose. Further, bacterial burden in the liver and spleen was significantly lower in mice treated with ADEP B315 compared to controls. In the MRSA experiments, ADEP B315 was able to significantly prolong survival compared to mice treated with either the vehicle (p = 0.001) or vancomycin (p = 0.007). ADEP B315 exhibited no significant toxicity in human whole blood cultures at concentrations up to 25 μg/ml.
conclusionsADEP B315 is safe and can cure mice that have lethal infections of methicillin-sensitive and -resistant strains of S. aureus.
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Registered trials
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