CLEC3A-Derived Antimicrobial Peptides Reduce Staphylococcus aureus Bacterial Counts in an In Vivo Biomaterial-Associated Infection Mouse Model

<b>Background/Objectives:</b> Biomaterials are an essential part of healthcare for both diagnostic and therapeutic procedures. Although some biomaterials possess antimicrobial properties, introducing biomaterial into the body may lead to infections due to bacterial adhesion on their surfaces and still poses a major clinical problem. Peptides derived from the human cartilage-specific C-type lectin domain family 3 member A (CLEC3A) show a potent antimicrobial effect. In addition, coating titanium, a commonly used prosthetic material, with the CLEC3A-derived AMPs HT-47 and WRK-30 greatly reduces the number of adherent bacteria in vitro. The aim of this study was to evaluate the effectiveness of CLEC3A-derived peptides HT-47 and WRK-30 in reducing bacterial adhesion and mitigating infection in vivo in a murine biomaterial-associated infection model. <b>Methods</b>: To do so, an in vivo mouse infection model was used, where titanium plates-either uncoated or coated with chimeric CLEC3A-derived peptides TiBP-HT-47 and TiBP-WRK-30-were implanted subcutaneously into mice. This was followed by the introduction of Staphylococcus aureus bacterial cultures to induce a biomaterial-associated infection. After 24 h, the titanium plates, surrounding tissue, and mice blood samples were investigated. <b>Results</b>: CLEC3A-coated titanium plates lead to a significantly lower bacterial count than uncoated ones. Additionally, they prevent the infection from spreading to the surrounding tissue. Moreover, mice with CLEC3A-coated implants display lower IL-6 serum levels and therefore decreased systemic inflammation. <b>Conclusions</b>: In conclusion, in this biomaterial-associated infection mouse-model, CLEC3A-derived peptides show in vivo antimicrobial activity by reducing bacterial burden on biomaterial and wound tissue and decreasing systemic inflammation, making them promising candidates for clinical applications.