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.

金黄色葡萄球菌是一种常见的病原体，可引起人和动物的临床和亚临床子宫内膜炎。在本研究中，设计的 DLP4 CSαβ 肽 ID13 在模拟胃液 (90.79%)、血清 (99.54%) 和不同 pH 缓冲液 (> 99%) 中对金黄色葡萄球菌CVCC 546 表现出高度稳定的抗菌活性和较低的细胞毒性。对小鼠子宫内膜上皮细胞 (MEECs) 的存活率比其亲本肽 DLP4 (74.14% 存活率) 高 89.62%。ID13 导致细菌膜去极化和参与膜电位维持和生物膜形成的基因表达下调。ID13体外药效分析显示与万古霉素、氨苄青霉素、利福平、环丙沙星有协同作用；细胞内抗微生物活性MEEC 中的金黄色葡萄球菌CVCC 546；以及抑制 RAW 264.7 中脂磷壁酸诱导的促炎细胞因子的能力。在金黄色葡萄球菌诱导的小鼠子宫内膜炎中，与万古霉素相似，ID13 显着缓解病理状况，抑制细胞因子（TNF-α、IL-1β、IL-6 和 IL-10）的产生，并抑制 TLR2- NF-κB 信号通路。总的来说，这些结果表明 ID13 可能是用于治疗金黄色葡萄球菌诱导的子宫内膜炎的潜在候选肽。