Therapeutic potential of a designed CSαβ peptide ID13 in Staphylococcus aureus-induced endometritis of mice.

Staphylococcus aureus is a common pathogen that can cause clinical and subclinical endometritis in humans and animals. In this study, a designed CSαβ peptide ID13 from DLP4 exhibited high stable antibacterial activity in simulated gastric fluid (90.79%), serum (99.54%), and different pH buffers (> 99%) against S. aureus CVCC 546 and lower cytotoxicity (89.62% viability) than its parent peptide DLP4 (74.14% viability) toward mouse endometrial epithelial cells (MEECs). ID13 caused a depolarization of bacterial membrane and downregulation of the expression of genes involved in membrane potential maintenance and biofilm formation. The in vitro efficacy analysis of ID13 showed a synergistic effect with vancomycin, ampicillin, rifampin, and ciprofloxacin; intracellular antimicrobial activity against S. aureus CVCC 546 in MEECs; and the ability to inhibit lipoteichoic acid-induced pro-inflammatory cytokines from RAW 264.7. In the S. aureus-induced endometritis of mice, similar to vancomycin, ID13 remarkably alleviated pathological conditions, inhibited the production of cytokines (TNF-α, IL-1ß, IL-6, and IL-10), and suppressed the TLR2-NF-κB signal pathway. Collectively, these results suggest that ID13 could be a potential candidate peptide for therapeutic application in S. aureus-induced endometritis. Key Points •Higher antibacterial activity and lower hemolysis of ID13 than DLP4. •ID13 could downregulate the genes of bacterial survival and infection. •ID13 could alleviate the S. aureus-induced endometritis of mice. •ID13 could regulate the cytokines and suppress the TLR2-NF-κB signal pathway.