Astragaloside IV as a potent vWbp inhibitor: An innovative strategy to mitigate foodborne Staphylococcus aureus infections

The rising threat of multidrug-resistant (MDR) pathogens, especially methicillin-resistant Staphylococcus aureus (MRSA), necessitates the development of novel antiinfective strategies. Staphylococcus aureus ( S. aureus ), a significant foodborne pathogen, secretes virulence factors that are crucial to its pathogenicity. Unlike conventional antibiotics, antivirulence strategies offer a promising approach by targeting these factors without inhibiting bacterial growth, thereby reducing selective pressure for resistance. Among these factors, von Willebrand factor-binding protein (vWbp) is a key contributor to S. aureus pathogenesis, mediating prothrombin activation and subsequent blood coagulation, which is vital for pathogen survival in the host. This study identified astragaloside IV (As-IV) a bioactive compound from traditional Chinese medicine, as a potent inhibitor of vWbp coagulase. As-IV effectively prolongs coagulation time and reduces S. aureus biotic matrix formation on surfaces relevant to food safety, such as catheters, in vitro . Mechanistic studies, including thermal shift assays (TSAs) and fluorescence quenching, revealed that As-IV directly binds to vWbp, attenuating its activity without altering protein expression levels. In vivo , As-IV exhibited protective effects in infection models, underscoring its potential as a virulence-targeted therapeutic. These findings significantly contribute to the advancement of antivirulence strategies and underscore the potential of As-IV in combating S. aureus infections. This paves the way for its broader application in enhancing public health measures and promoting innovative therapeutic approaches.