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- Title
Antibacterial activity and mechanisms of D-3263 against Staphylococcus aureus.
- Authors
Liu, Xiaoju; Xiong, Yanpeng; Peng, Renhai; Zhang, Yufang; Cai, Shuyu; Deng, Qiwen; Yu, Zhijian; Wen, Zewen; Chen, Zhong; Hou, Tieying
- 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.
- Publication
BMC Microbiology, 2024, Vol 24, Issue 1, p1
- ISSN
1471-2180
- Publication type
Article
- DOI
10.1186/s12866-024-03377-3