Pacin, a novel bacteriocin from Pseudomonas strain 166, exhibits anti-MRSA activity with low toxicity and high therapeutic potential

The emergence and rapid spread of methicillin-resistant Staphylococcus aureus (MRSA) pose a significant threat to public health, underscoring the urgent need for the development of effective antibacterial agents. Bacteriocins, as highly promising antibacterial candidates, have garnered considerable attention in the scientific community. In this study, a novel bacteriocin, designated Pacin, was successfully purified from the fermentation broth of Pseudomonas strain 166. Pacin exhibited potent antibacterial activity against MRSA, with minimum inhibitory concentration (MIC) of 0.25 µg/mL. At concentrations up to 512 µg/mL, Pacin showed no significant cytotoxicity toward Vero or F81 cells and induced negligible hemolysis of rabbit red blood cells, with a hemolytic rate below 0.04%. In a murine model of MRSA-infected wounds, Pacin significantly promoted wound healing. In a peritonitis-sepsis model, mice treated with Pacin displayed no organ abnormalities and a marked reduction in bacterial burden. Further analyses, including cell membrane integrity assays, cell wall integrity assessments, scanning electron microscopy, and transmission electron microscopy, demonstrated that Pacin exerts its antibacterial effect by disrupting the bacterial cell membrane and cell wall structures, thereby inhibiting bacterial survival. Collectively, these findings establish Pacin as a highly effective antibiotic alternative for combating MRSA infections, with substantial potential for clinical application.

IMPORTANCE

This study introduces Pacin, a novel bacteriocin isolated from Pseudomonas strain 166, as a potent therapeutic agent against MRSA. With the global rise of antibiotic resistance threatening public health, there is an urgent need for safe and effective alternatives to conventional drugs. Pacin demonstrates exceptional activity by effectively killing MRSA through membrane and cell wall disruption while showing no toxicity to mammalian cells or zebrafish embryos. Its stability under varying environmental conditions and shows efficacy in treating severe skin infections and sepsis in animal models highlight its clinical potential. These findings position Pacin as a promising next-generation antimicrobial agent capable of addressing critical gaps in current treatment strategies for life-threatening resistant infections.