Synthetic Antibacterial Quaternary Phosphorus Salts Promote Methicillin-Resistant Staphylococcus aureus-Infected Wound Healing

Liang-Wen Shi,1,* Quan-Quan Zhuang,2,* Tai-Qin Wang,1 Xian-Dong Jiang,3 Yue Liu,4 Jing-Wen Deng,1 Huan-Huan Sun,5 Yi Li,4 Hao-Hong Li,4 Ting-Bo Liu,6 Jian-Zhi Liu1 1Department of Otorhinolaryngology, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China; 2Department of Pharmacy, Affiliated Quanzhou First Hospital of Fujian Medical University, Quanzhou, Fujian, People’s Republic of China; 3Department of laboratory medicine, the School of Medical Technology and Engineering, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 4College of Chemistry, Fuzhou University, Fuzhou, Fujian, People’s Republic of China; 5Department of Otolaryngology, Changji Region Hospital of Traditional Chinese Medicine, Changji, Xinjiang, People’s Republic of China; 6Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian-Zhi Liu, Department of Otorhinolaryngology, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China, Tel/Fax +86-591 83346181, Email liujianzhient@163.com Ting-Bo Liu, Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China, Tel/Fax +86-591 83357896, Email liutingboblood@163.comBackground: Drug-resistant microbes pose a global health concern, requiring the urgent development of effective antibacterial agents and strategies in clinical practice. Therefore, there is an urgent need to explore novel antibacterial materials to effectively eliminate bacteria. The synthesis of quaternary phosphonium salt in haloargentate systems, wherein the phosphorus atom is represented in a cationic form, is a possible strategy for the development of antibacterial materials.Methods: Using (triphenyl)phosphonium-based quaternary phosphorus salts with different spacer lengths (n=2, 4, 6) as a template, we designed three kinds of quaternary phosphorus salts as effective antibacterial agents against drug-resistant bacteria.Results: The synthesized quaternary phosphorus salt of (1,4-DBTPP)Br2 effectively prevented the formation of the bacterial biofilms, and degraded bacterial membranes and cell walls by promoting the production of reactive oxygen species, which exhibited effective therapeutic effects in a rat model of a superficial wound infected with methicillin-resistant Staphylococcus aureus.Conclusion: The quaternary phosphorus salt (1,4-DBTPP)Br2 demonstrated hemocompatibility and low toxicity, revealing its potential in the treatment of clinical infections.Graphical Abstract: Keywords: quaternary phosphorus salts, reactive oxygen species, antibacterial, biocompatible, wound infection therapy