2. Academic Validation
  3. Antibacterial activity and mechanisms of D-3263 against Staphylococcus aureus

Antibacterial activity and mechanisms of D-3263 against Staphylococcus aureus

  • BMC Microbiol. 2024 Jun 26;24(1):224. doi: 10.1186/s12866-024-03377-3.
Xiaoju Liu # 1,  Yanpeng Xiong # 1,  Renhai Peng # 1,  Yufang Zhang 2,  Shuyu Cai 1 3,  Qiwen Deng 1 3,  Zhijian Yu 1 3,  Zewen Wen 1 3,  Zhong Chen 4 5,  Tieying Hou 6 7
Affiliations

Affiliations

  • 1 Department of Infectious Diseases, Shenzhen Key Laboratory for Endogenous Infection, Huazhong University of Science and Technology Union Shenzhen Hospital, No 89, Taoyuan Road, Nanshan District, Shenzhen, 518052, China.
  • 2 Department of Biology, Washington University in St. Louis, 1 Brookings Drive, St Louis, MO, 63130, USA.
  • 3 Department of Infectious Diseases and Shenzhen key Laboratory of Endogenous infection, Shenzhen Nanshan People's Hospital and the 6th Affiliated Hospital of Shenzhen University Medical School, No 89, Taoyuan Road, Nanshan District, Shenzhen, 518052, China.
  • 4 Department of Infectious Diseases, Shenzhen Key Laboratory for Endogenous Infection, Huazhong University of Science and Technology Union Shenzhen Hospital, No 89, Taoyuan Road, Nanshan District, Shenzhen, 518052, China. cchen17@fudan.edu.cn.
  • 5 Department of Infectious Diseases and Shenzhen key Laboratory of Endogenous infection, Shenzhen Nanshan People's Hospital and the 6th Affiliated Hospital of Shenzhen University Medical School, No 89, Taoyuan Road, Nanshan District, Shenzhen, 518052, China. cchen17@fudan.edu.cn.
  • 6 Department of Infectious Diseases, Shenzhen Key Laboratory for Endogenous Infection, Huazhong University of Science and Technology Union Shenzhen Hospital, No 89, Taoyuan Road, Nanshan District, Shenzhen, 518052, China. sz_houtieying@yeah.net.
  • 7 Department of Infectious Diseases and Shenzhen key Laboratory of Endogenous infection, Shenzhen Nanshan People's Hospital and the 6th Affiliated Hospital of Shenzhen University Medical School, No 89, Taoyuan Road, Nanshan District, Shenzhen, 518052, China. sz_houtieying@yeah.net.
  • # Contributed equally.
PMID: 38926818 DOI: 10.1186/s12866-024-03377-3
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.

Keywords

Staphylococcus aureus; Antibacterial activity; Biofilm; D-3263; Phospholipids.

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