Therapeutic Potential of Insect Defensin DLP4 Against Staphylococcus hyicus-Infected Piglet Exudative Epidermitis

<b>Background/Objectives</b>: The emergence of resistance to <i>Staphylococcus hyicus</i> (<i>S. hyicus</i>), the major cause of exudative epidermatitis (EE) in piglets, has led to the need for new antimicrobial agents. The study aimed to evaluate the potential efficacy of the insect defensin DLP4 against EE in piglets caused by clinically isolated <i>S. hyicus</i> ACCC 61734. <b>Methods and Results</b>: DLP4 showed strong antibacterial activity against <i>S. hyicus</i> ACCC 61734 (minimum inhibitory concentration, MIC: 0.92 μM, median effect concentration, EC₅₀: 3.158 μM). DLP4 could effectively inhibit the formation of <i>S. hyicus</i> early biofilm with an inhibition rate of 95.10-98.34% and eradicate mature biofilm with a clearance rate of 82.09-86.41%, which was significantly superior to that of ceftriaxone sodium (CRO). Meanwhile, DLP4 could efficiently inhibit bacteria in early and mature biofilm, killing up to 95.3% of bacteria in early biofilm and 87.2-90.3% of bacteria in mature biofilm. The results showed that DLP4 could be effective in alleviating the clinical symptoms of EE by down-regulating the nuclear factor κB (NF-κB) signaling pathway, balancing cytokines, inhibiting bacterial proliferation, and reducing organ tissue damage. <b>Conclusions</b>: This study firstly demonstrated the potential efficacy of DLP4 against EE caused by <i>S. hyicus</i> ACCC 61734 infection in piglets, which may be used as an alternative to antibiotics in treating EE.