PDF(Pubmed)
Abstract：
Intracellular pathogens including Staphylococcus aureus contribute to the non-healing phenotype of chronic wounds. Lactobacilli, well known as beneficial bacteria, are also reported to modulate the immune system, yet their role in cutaneous immunity remains largely unknown. We explored the therapeutic potential of bacteria-free postbiotics, bioactive lysates of lactobacilli, to reduce intracellular S. aureus colonization and promote healing. Fourteen postbiotics derived from various lactobacilli species were screened, and Latilactobacillus curvatus BGMK2-41 was selected for further analysis based on the most efficient ability to reduce intracellular infection by S. aureus diabetic foot ulcer clinical isolate and S. aureus USA300. Treatment of both infected keratinocytes in vitro and infected human skin ex vivo with BGMK2-41 postbiotic cleared S. aureus. Keratinocytes treated in vitro with BGMK2-41 upregulated expression of antimicrobial response genes, of which DEFB4, ANG, and RNASE7 were also found upregulated in treated ex vivo human skin together with CAMP exclusively upregulated ex vivo. Furthermore, BGMK2-41 postbiotic treatment has a multifaceted impact on the wound healing process. Treatment of keratinocytes stimulated cell migration and the expression of tight junction proteins, while in ex vivo human skin BGMK2-41 increased expression of anti-inflammatory cytokine IL-10, promoted re-epithelialization, and restored the epidermal barrier via upregulation of tight junction proteins. Together, this provides a potential therapeutic approach for persistent intracellular S. aureus infections.
摘要：
包括金黄色葡萄球菌在内的细胞内病原体有助于慢性伤口的非愈合表型。乳酸杆菌,众所周知的有益细菌，据报道还可以调节免疫系统，然而，它们在皮肤免疫中的作用仍然很大程度上未知。我们探索了无细菌后生物的治疗潜力，乳酸菌的生物活性裂解物，减少细胞内金黄色葡萄球菌定植并促进愈合。筛选了来自各种乳杆菌物种的14种博士后，基于降低金黄色葡萄球菌糖尿病足溃疡临床分离株和金黄色葡萄球菌USA300的细胞内感染的最有效能力,选择弯曲乳杆菌BGMK2-41用于进一步分析。用BGMK2-41后生物清除的金黄色葡萄球菌处理体外感染的角质形成细胞和离体感染的人皮肤。体外用BGMK2-41处理的角质形成细胞上调抗微生物反应基因的表达，其中DEFB4，ANG，还发现RNASE7在经处理的离体人皮肤中上调,同时CAMP在离体唯一上调。此外，BGMK2-41后生物治疗对伤口愈合过程具有多方面的影响。角质形成细胞的处理刺激细胞迁移和紧密连接蛋白的表达，而在离体人皮肤BGMK2-41中，抗炎细胞因子IL-10的表达增加，促进上皮再形成，并通过上调紧密连接蛋白来恢复表皮屏障。一起,这为持续性细胞内金黄色葡萄球菌感染提供了潜在的治疗方法.
