Department of Molecular Medicine and Surgery, Section of Reconstructive Plastic Surgery, Karolinska Institutet, Stockholm, Sweden.
APMIS. 2012 Oct;120(10):786-93. doi: 10.1111/j.1600-0463.2012.02907.x. Epub 2012 May 7.
A novel murine experimental wound infection model was used to assess the efficacy of multi-component immunization against Staphylococcus aureus infection. Necrotic lesions were induced in mice with venom from Bothrops asper and infected with a low inoculum, 1 × 10(2) CFU. The wound infection model therefore more resembles a clinical case of S. aureus infection compared with conventional infection models where far more bacteria are required. Before infection, mice were immunized with four recombinant S.aureus proteins expressed from Escherichia coli: (i) domains 1-3 of Extracellular adherence protein (Eap), (ii) Efb - D (fusion protein combining Extracellular fibrinogen binding protein (Efb) and a fibronectin binding domain (D) of the fibronectin binding protein (FnBP) and (iii) clumping factor A (ClfA). In the immunized group, lower bacterial colonization, undisturbed crust formation and significantly faster wound healing were found compared with the unimmunized control group. Efb and Eap have previously been found to impair wound healing and neutralization of these proteins by antibodies restores a more natural wound healing process. This effect is further also enhanced by the proposed opsonic activity of antibodies against ClfA and FnBP.
采用新型鼠实验性伤口感染模型评估了针对金黄色葡萄球菌感染的多组分免疫的疗效。用矛头蝮蛇毒液诱导小鼠产生坏死病变，并以低接种量（1×102 CFU）感染。与传统感染模型相比，该伤口感染模型更类似于金黄色葡萄球菌感染的临床病例，因为传统感染模型需要更多的细菌。在感染之前，用从大肠杆菌表达的四种重组金黄色葡萄球菌蛋白对小鼠进行免疫：（i）细胞外黏附蛋白（Eap）的结构域 1-3，（ii）Efb-D（将细胞外纤维蛋白结合蛋白（Efb）和纤维连接蛋白结合蛋白（FnBP）的纤维连接蛋白结合结构域（D）融合而成的融合蛋白）和（iii）聚集因子 A（ClfA）。与未免疫对照组相比，免疫组中发现细菌定植减少、不受干扰的结痂形成和伤口愈合明显加快。先前发现 Efb 和 Eap 会损害伤口愈合，并且抗体对这些蛋白质的中和作用可恢复更自然的伤口愈合过程。针对 ClfA 和 FnBP 的抗体的拟补体活性进一步增强了这种作用。
