Staphylococcus aureus resistance to albocycline can be achieved by mutations that alter cellular NAD/PH pools
| Autor: | Catherine L. Grimes, Paul M. Dunman, Elizabeth A. D'Ambrosio, Samer S. Daher, Rodrigo B. Andrade, Tyler Scherzi |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Staphylococcus aureus
Clinical Biochemistry Pharmaceutical Science Microbial Sensitivity Tests medicine.disease_cause 01 natural sciences Biochemistry Ribosome Article Biological pathway chemistry.chemical_compound Lactones Structure-Activity Relationship Downregulation and upregulation Drug Discovery medicine Molecular Biology Natural product Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Organic Chemistry Vancomycin Resistance Small molecule 0104 chemical sciences Anti-Bacterial Agents 010404 medicinal & biomolecular chemistry chemistry Mechanism of action Molecular Medicine Methicillin Resistance NAD+ kinase medicine.symptom NADP |
| Zdroj: | Bioorg Med Chem |
| Popis: | Small molecule target identification is a critical step in modern antibacterial drug discovery, particularly against multi-drug resistant pathogens. Albocycline (ALB) is a macrolactone natural product with potent activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) whose mechanism of action has been elusive to date. Herein, we report biochemical and genomic studies that reveal ALB does not target bacterial peptidoglycan biosynthesis or the ribosome; rather, it appears to modulate NADPH ratios and upregulate redox sensing in the cell consistent with previous studies at Upjohn. Owing to the complexity inherent in biological pathways, further genomic assays are needed to identify the true molecular target(s) of albocycline. |
| Databáze: | OpenAIRE |
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