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

Abstract

Background: 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.