The inhibitory effect of extracellular vesicles derived from S. epidermidis on MRSA biofilms

The biofilm formed by methicillin-resistant Staphylococcus aureus (MRSA) on orthopedic implants substantially impedes the penetration of antimicrobial agents, leading to recurrent bone infections and imposing a significant financial burden on patients. Prior research has demonstrated that Staphylococcus epidermidis, a conditional pathogen, exhibits low toxicity in deep tissues and effectively suppresses MRSA growth in superficial tissues. However, the mechanism by which S. epidermidis inhibits MRSA, as well as its capacity to suppress MRSA proliferation or biofilm formation in deep tissues, requires further elucidation. This study hypothesizes that S. epidermidis extracellular vesicles (SE-EVs) may play a pivotal regulatory role in this process. To validate this hypothesis, we obtained SE-EVs and observed the biological effects of the vesicles on MRSA. In vitro experimental results revealed that SE-EVs markedly inhibited MRSA proliferation and biofilm formation. Furthermore, in vivo experiments demonstrated that SE-EVs at a concentration of 1 μg/mL effectively suppressed MRSA-associated implant infections and biofilm formation. We further elucidated the primary mechanism by which SE-EVs inhibit MRSA biofilms through RNA sequencing. The sequencing results suggested that this effect is achieved by suppressing the cationic antimicrobial peptide (CAMP) resistance signaling pathway, which plays a critical role in biofilm formation. Additionally, both in vitro and in vivo experiments confirmed that SE-EVs do not induce inflammation or cause damage to vital organs. In summary, this study is the first to reveal the natural anti-MRSA biofilm properties of SE-EVs, providing a theoretical foundation for their potential application in treating MRSA-associated implant bone infections.