Rapid release of high-valent silver ions from water-soluble porphyrin complexes to enhance the direct killing of Methicillin-Resistant Staphylococcus aureus

Abstract

The emergence of multidrug-resistant (MDR) bacteria represented by MRSA (Methicillin-resistant Staphylococcus aureus) poses a great challenge to current anti-infection treatment. It is critical to develop efficient MRSA anti-bacteria drugs and explore simple therapeutic strategies with low MDR risk. Herein, we synthesized high-valent (Ag^II/Ag^III) water-soluble porphyrins (cationic AgTMPyP and anionic AgTMPPS) and investigated their direct bactericidal property for MRSA without photoactivation in vitro and in vivo. The cationic porphyrin AgTMPyP exhibits well oxidase-like activity and has 100 % sterilizing rate at 8 μmol/L concentration. Besides, AgTMPyP can effectively destroy biofilms in vitro, mediate the polarization of macrophages from M1 to M2, and promote wound healing in vivo. Combined with DFT calculation, the related antibacterial mechanism is further discussed. High-valent silverporphyrins can maintain stable in water for at least 200 days. The moment they encounter MRSA, high-valent silver ions from AgTMPyP can be immediately released from the porphyrin ring and attack the MRSA with efficient sterilization. Together with the hemolysis, blood routine and blood biochemistry tests, it is proved that AgTMPyP can have great prospects in the direct treatment of bacterial infections in skin diseases in the future.

Statement of significance

The emergence of multidrug-resistant (MDR) bacteria represented by MRSA poses a great challenge to current anti-infection treatment. It has become critical to develop efficient MRSA anti-bacteria drugs and explore simple therapeutic strategies with low MDR risk. We synthesized high-valent (Ag^II/Ag^III) water-soluble silver porphyrins (AgTMPyP and AgTMPPS), which can be stable for long periods in aqueous solutions. AgTMPyP can directly and efficiently kill bacteria and destroy biofilms without photoactivation in vitro and in vivo. Combined with DFT calculation, the related antibacterial mechanism is further discussed. AgTMPyP is a superior antimicrobial agent with good biocompatibility and it can have great prospects in the direct treatment of bacterial infections and wound healing in the future.