Project description:In order to determine the mechanism of Cajanin Stilbene Acid inhibiting vancomycin-resistant enterococci, we compared the changes in protein expression of enterococci V583 strain before and after treated by Cajanin Stilbene Acid.
Project description:Cervimycins A‒D are natural products of Streptomyces tendae HKI 0179 with promising activity against multidrug resistant staphylococci and vancomycin resistant enterococci. To initiate mode of action studies, we selected cervimycin C and D resistant (CmR) Staphylococcus aureus strains. Genome sequencing of CmR mutants revealed amino acid exchanges in the essential histidine kinase WalK, the Clp protease proteolytic subunit ClpP or the Clp ATPase ClpC, and the heat shock protein DnaK. Proteomic analysis revealed massive alterations in CmR-02 (amino acid exchanges: ClpP-I29F, DnaK-A112P, WalK-A243V) compared to the parent strain S. aureus SG511 Berlin, with major modifications in the heat shock regulon, the metal ion homeostasis and the carbohydrate metabolism. These effects were alleviated in the antibiotic susceptible suppressor mutant 02REV (amino acid exchanges: ClpP-I29F/M31I, WalK-A243V/S191L).
2022-09-22 | PXD034970 | Pride
Project description:Vancomycin-resistant enterococci in Southern Denmark
Project description:The authors use a large dataset (>30k) to train an explainable graph-based model to identify potential antibiotics with low cytotoxicity. The model uses a substructure-based approach to explore the chemical space. Using this method, they were able to screen 283 compounds and identify a candidate active against methicillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococci.
Model Type: Predictive machine learning model.
Model Relevance: Prediction of Human cytotoxicity endpoints.
Model Encoded by: Sarima Chiorlu (Ersilia)
Metadata Submitted in BioModels by: Zainab Ashimiyu-Abdusalam
Implementation of this model code by Ersilia is available here:
https://github.com/ersilia-os/eos42ez
Project description:The authors use a large dataset (>30k) to train an explainable graph-based model to identify potential antibiotics with low cytotoxicity. The model uses a substructure-based approach to explore the chemical space. Using this method, they were able to screen 283 compounds and identify a candidate active against methicillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococci.
Model Type: Predictive machine learning model.
Model Relevance: The model predicts the probability of growth inhibition.
Model Encoded by: Sarima Chiorlu (Ersilia)
Metadata Submitted in BioModels by: Zainab Ashimiyu-Abdusalam
Implementation of this model code by Ersilia is available here:
https://github.com/ersilia-os/eos18ie
Project description:Resistance to antibiotics is an emerging problem and necessitates novel antibacterial therapies. Cervimycins A‒D are natural products of Streptomyces tendae HKI 0179 with promising activity against multidrug resistant staphylococci and vancomycin resistant enterococci. We studied the mode of action of cervimycin C and D by selection of cervimycin resistant (CmR) Staphylococcus aureus strains. Genome sequencing of CmR mutants revealed amino acid exchanges in the essential histidine kinase WalK, the Clp protease proteolytic subunit ClpP or the Clp ATPase ClpC, and the heat shock protein DnaK. Interestingly, all characterized cervimycin resistant mutants harbored a combination of mutations in walK and clpP or clpC. Mutations in the Clp system abolished ClpP or ClpC activity, and the deletion of clpP rendered S. aureus but not B. subtilis cervimycin resistant. The essential gene walK was the second mutational hotspot in the cervimycin resistant S. aureus mutants, which decreased WalK activity in vitro and generated a vancomycin intermediately resistant phenotype, with a thickened cell wall, a slower growth rate, and reduced cell lysis. Transcriptomic and proteomic analysis revealed massive alterations in the CmR strains , with major alterations in the heat shock regulon, the metal ion homeostasis and the carbohydrate metabolism. Taken together, compensatory mutations in cervimycin resistant mutants induced a VISA phenotype in S. aureus, suggesting cell wall metabolism or the ClpCP proteolytic system as primary target of the polyketide antibiotic