Antibacterial activity and mechanisms of D-3263 against Staphylococcus aureus

Xiaoju Liu; Yanpeng Xiong; Renhai Peng; Yufang Zhang; Shuyu Cai; Qiwen Deng; Zhijian Yu; Zewen Wen; Zhong Chen; Tieying Hou

doi:10.1186/s12866-024-03377-3

BMC Microbiology (Jun 2024)

Antibacterial activity and mechanisms of D-3263 against Staphylococcus aureus

Xiaoju Liu,
Yanpeng Xiong,
Renhai Peng,
Yufang Zhang,
Shuyu Cai,
Qiwen Deng,
Zhijian Yu,
Zewen Wen,
Zhong Chen,
Tieying Hou

Affiliations

Xiaoju Liu: Department of Infectious Diseases, Shenzhen Key Laboratory for Endogenous Infection, Huazhong University of Science and Technology Union Shenzhen Hospital
Yanpeng Xiong: Department of Infectious Diseases, Shenzhen Key Laboratory for Endogenous Infection, Huazhong University of Science and Technology Union Shenzhen Hospital
Renhai Peng: Department of Infectious Diseases, Shenzhen Key Laboratory for Endogenous Infection, Huazhong University of Science and Technology Union Shenzhen Hospital
Yufang Zhang: Department of Biology, Washington University in St. Louis
Shuyu Cai: Department of Infectious Diseases, Shenzhen Key Laboratory for Endogenous Infection, Huazhong University of Science and Technology Union Shenzhen Hospital
Qiwen Deng: Department of Infectious Diseases, Shenzhen Key Laboratory for Endogenous Infection, Huazhong University of Science and Technology Union Shenzhen Hospital
Zhijian Yu: Department of Infectious Diseases, Shenzhen Key Laboratory for Endogenous Infection, Huazhong University of Science and Technology Union Shenzhen Hospital
Zewen Wen: Department of Infectious Diseases, Shenzhen Key Laboratory for Endogenous Infection, Huazhong University of Science and Technology Union Shenzhen Hospital
Zhong Chen: Department of Infectious Diseases, Shenzhen Key Laboratory for Endogenous Infection, Huazhong University of Science and Technology Union Shenzhen Hospital
Tieying Hou: Department of Infectious Diseases, Shenzhen Key Laboratory for Endogenous Infection, Huazhong University of Science and Technology Union Shenzhen Hospital

DOI: https://doi.org/10.1186/s12866-024-03377-3
Journal volume & issue: Vol. 24, no. 1
pp. 1 – 12

Abstract

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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.

Published in BMC Microbiology

ISSN: 1471-2180 (Online)
Publisher: BMC
Country of publisher: United Kingdom
LCC subjects: Science: Microbiology
Website: http://www.biomedcentral.com/bmcmicrobiol/

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