Effects of cyclotides against cutaneous infections caused by Staphylococcus aureus

The main bacterium associated with skin infection is Staphylococcus aureus, occurring especially in infections acquired via surgical wounds, commonly leading to lethal hospital-acquired infections, emphasizing the importance of identifying new antimicrobial compounds. Among them, cyclotides have gained interest due to their high stability and multifunctional properties. Here, cycloviolacin 2 (CyO2) and kalata B2 (KB2) were evaluated to determinate their anti-staphylococcal activities using a subcutaneous infection model. Anti-staphylococcal activities of 50mM for KB2 and 25mM for CyO2 were detected with no cytotoxic activities against RAW 264.7 monocytes. In the in vivo assays, both cyclotides reduced bacterial load and CyO2 demonstrated an increase in the phagocytosis index, suggesting that the CyO2 in vivo anti-staphylococcal activity may be associated with phagocytic activity, additionally to direct anti-pathogenic activity.