Novartis Vaccines, Research Center, Siena, Italy.
J Infect Dis. 2012 Oct 1;206(7):1041-9. doi: 10.1093/infdis/jis463. Epub 2012 Jul 24.
Iron availability plays an essential role in staphylococcal pathogenesis. We selected FhuD2, a lipoprotein involved in iron-hydroxamate uptake, as a novel vaccine candidate against Staphylococcus aureus. Unprecedented for staphylococcal lipoproteins, the protein was demonstrated to have a discrete, punctate localization on the bacterial surface. FhuD2 vaccination generated protective immunity against diverse clinical S. aureus isolates in murine infection models. Protection appeared to be associated with functional antibodies that were shown to mediate opsonophagocytosis, to be effective in passive transfer experiments, and to potentially block FhuD2-mediated siderophore uptake. Furthermore, the protein was found to be up-regulated in infected tissues and was required for staphylococcal dissemination and abscess formation. Herein we show that the staphylococcal iron-hydroxamate uptake system is important in invasive infection and functions as an efficacious vaccine target.
铁元素的可利用性在葡萄球菌的发病机制中起着至关重要的作用。我们选择 FhuD2（一种参与铁-羟肟酸盐摄取的脂蛋白）作为针对金黄色葡萄球菌的新型疫苗候选物。这种脂蛋白在葡萄球菌中是前所未有的，其在细菌表面呈现离散的点状定位。FhuD2 疫苗接种在小鼠感染模型中针对多种临床分离的金黄色葡萄球菌产生了保护性免疫。这种保护似乎与功能性抗体有关，这些抗体被证明可以介导调理吞噬作用，在被动转移实验中有效，并可能阻止 FhuD2 介导的铁载体摄取。此外，还发现该蛋白在感染组织中上调，并需要其进行葡萄球菌的传播和脓肿形成。本研究表明，葡萄球菌的铁-羟肟酸盐摄取系统在侵袭性感染中很重要，并且可以作为有效的疫苗靶标。
