AI Article Synopsis
- Multi-drug-resistant Staphylococcus aureus infections highlight the urgent need for new antibiotics, with D-3263 showing promise as a TRPM8 agonist with potential antibacterial properties.
- D-3263 demonstrated strong bactericidal effects on clinical strains of methicillin-resistant S. aureus (MRSA) and Enterococcus faecalis, with effective inhibition of bacterial biofilms at subinhibitory levels and complete clearance at higher doses.
- Proteomic analysis indicated that D-3263 impacts amino acid biosynthesis and carbohydrate metabolism in bacteria, while also increasing the permeability of their membranes, suggesting it targets the bacterial cell membrane for its antibacterial action.
Article Abstract
Multi-drug-resistant Staphylococcus aureus infections necessitate novel antibiotic development. D-3263, a transient receptor potential melastatin member 8 (TRPM8) agonist, has potential antineoplastic properties. Here, we reported the antibacterial and antibiofilm activities of D-3263. Minimum inhibitory concentrations (MICs) against S. aureus, Enterococcus faecalis and E. faecium were ≤ 50 µM. D-3263 exhibited bactericidal effects against clinical methicillin-resistant S. aureus (MRSA) and E. faecalis strains at 4× MIC. Subinhibitory D-3263 concentrations effectively inhibited S. aureus and E. faecalis biofilms, with higher concentrations also clearing mature biofilms. Proteomic analysis revealed differential expression of 29 proteins under 1/2 × MIC D-3263, influencing amino acid biosynthesis and carbohydrate metabolism. Additionally, D-3263 enhanced membrane permeability of S. aureus and E. faecalis. Bacterial membrane phospholipids phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and cardiolipin (CL) dose-dependently increased D-3263 MICs. Overall, our data suggested that D-3263 exhibited potent antibacterial and antibiofilm activities against S. aureus by targeting the cell membrane.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11201875 | PMC |
| http://dx.doi.org/10.1186/s12866-024-03377-3 | DOI Listing |
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