Staphylococcus aureus (S. aureus), especially methicillin‐resistant S. aureus (MRSA), causes wound infections, whose treatment remains a clinical challenge. Bacterium‐infected wounds often create acidic niches with a pH 4.5–6.5. Endolysin LysSYL, which is derived from phage SYL, shows promise as an antistaphylococcal agent. However, endolysins generally exhibit instability and possess low bioavailability in acidic microenvironments. Here, an array of self‐assembling peptides is designed, and peptide L5 is screened out based on its gel formation property and bioavailability. L5 exerted a pH‐switchable antimicrobial effect (pH 5.5) and formed biocompatible hydrogels at neutral pH (pH 7.4). The LysSYL‐loaded L5 can assemble L5@LysSYL hydrogels, increase thermal stability, and exhibit the slow‐release effect of LysSYL. Effective elimination of S. aureus is achieved by L5@LysSYL through bacterial membrane disruption and cell separation inhibition. Moreover, L5@LysSYL hydrogels exhibit great potential in promoting wound healing in a mouse wound model infected by MRSA. Furthermore, L5@LysSYL hydrogels are safe and can decrease the cytokine levels and increase the number of key factors for vessel formation, which contribute to wound healing. Overall, the self‐assembling L5@LysSYL can effectively clean MRSA and promote wound healing, which suggests its potential as a pH‐sensitive wound dressing for the management of wound infections.

中文翻译：

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载有 LysSYL 的 pH 值开关自组装肽水凝胶可促进耐甲氧西林金黄色葡萄球菌的消除和伤口愈合


金黄色葡萄球菌 （S. aureus），尤其是耐甲氧西林金黄色葡萄球菌 （MRSA），可引起伤口感染，其治疗仍然是一个临床挑战。细菌感染的伤口通常会产生 pH 值为 4.5-6.5 的酸性生态位。来源于噬菌体 SYL 的溶血素 LysSYL 有望作为抗葡萄球菌剂。然而，内溶素通常在酸性微环境中表现出不稳定性并且具有低生物利用度。在这里，设计了一系列自组装肽，并根据其凝胶形成特性和生物利用度筛选出肽 L5。L5 发挥 pH 值可切换的抗菌作用 （pH 5.5），并在中性 pH 值 （pH 7.4） 下形成生物相容性水凝胶。负载 LysSYL 的 L5 可以组装L5@LysSYL水凝胶，提高热稳定性，并表现出 LysSYL 的缓释作用。通过细菌膜破坏和细胞分离抑制进行L5@LysSYL，可以有效消除金黄色葡萄球菌。此外，L5@LysSYL 水凝胶在促进 MRSA 感染的小鼠伤口模型中的伤口愈合方面表现出巨大潜力。此外，L5@LysSYL水凝胶是安全的，可以降低细胞因子水平并增加血管形成的关键因素的数量，这有助于伤口愈合。总体而言，自组装L5@LysSYL可以有效清洁 MRSA 并促进伤口愈合，这表明它有可能作为 pH 敏感伤口敷料来管理伤口感染。