Temporin-derived peptides promote MRSA-infected wound healing and protect mice from MRSA-induced pneumonia.

Methicillin-resistant Staphylococcus aureus (MRSA) causes life-threatening skin and systemic infections, necessitating novel antimicrobial strategies. The Temporin-GHb (GHb) derived peptides GHbR, GHbK, GHb3K, GHb11K, and GHbK4R were demonstrated effective bactericidal activity against both planktonic and biofilm state of MRSA, without inducing detectable bacterial resistance in vitro. Additionally, the peptides have high biocompatibility, with GHb3K exhibiting the lowest cytotoxicity in HaCaT cells and promoting cell migration. In vivo, GHbR and GHb3K effectively accelerated MRSA-infected skin wound healing by reducing bacterial burden, suppressing pro-inflammatory cytokines, and promoting tissue regeneration and remodeling. In mouse model of MRSA pneumonia, they reduced bacterial loads, mitigated lung inflammation, and accelerated pulmonary tissue recovery. These findings highlight the therapeutic potential of Temporin-derived peptides as promising alternatives for combating MRSA infections.