Development of TPP-HK conjugates as membrane-targeting antibacterial agents against methicillin-resistant...

The emergence of methicillin-resistant Staphylococcus aureus (MRSA) greatly threatens human health. Here, a series of TPP-HK conjugates with potent bacterial cytoplasmic membrane-targeting capabilities were developed to combat the escalating threat of MRSA infections. Among them, TH16 showed excellent antibacterial activity and low frequency resistance. Mechanistic studies revealed that TH16 destroyed the bacterial cytoplasmic membrane and increased the levels of intracellular ROS, resulting in bacterial death. Our study demonstrates that TPP-HK conjugates as membrane-targeting agents could be a promising therapeutic strategy against MRSA infections.