Pan-Ras-In-1 triggers cell wall lysis to eradicate Staphylococcus aureus

Given the global crisis of antimicrobial resistance, the dual anticancer and antibacterial properties of certain agents have attracted increasing attention as a potential alternative to conventional antimicrobial approaches. In this study, we characterized the bactericidal activity of an anticancer molecule (Pan-Ras-In-1) against Staphylococcus aureus, a pathogen associated with refractory infection. In vitro assays revealed that Pan-Ras-In-1 has a more pronounced bactericidal effect on S. aureus cells than the traditional antibiotics vancomycin and levofloxacin. Furthermore, Pan-Ras-In-1 displayed potential therapeutic efficacy in vivo, as assessed using the murine systemic infection and skin abscess models, suggesting its potential for subsequent clinical applications. Exposure of S. aureus to Pan-Ras-In-1 activates CidA-associated peptidoglycan hydrolase systems, which partially mediate bacterial programmed cell death. Peptide-centric local stability analyses revealed that Pan-Ras-In-1 binds to TarA protein, suppressing wall teichoic acid polymer production. The combined action of two mechanisms enables Pan-Ras-In-1 to compromise bacterial cell wall integrity.