IsdA and IsdB antibodies protect mice against Staphylococcus aureus abscess formation and lethal challenge.

IsdA and IsdB antibodies protect mice against Staphylococcus aureus abscess formation and lethal challenge.
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DOI:
10.1016/j.vaccine.2010.02.097
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发表时间:
2010-08-31
期刊:
影响因子:
5.5
通讯作者:
Schneewind, Olaf
Schneewind, Olaf
中科院分区:
医学3区
文献类型:
--
作者:
Kim, Hwan Keun;DeDent, Andrea;Cheng, Alice G.;McAdow, Molly;Bagnoli, Fabio;Missiakas, Dominique M.;Schneewind, Olaf

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金黄色葡萄球菌是菌血症和医院获得性感染的最常见原因,然而,目前还没有预防葡萄球菌疾病的疫苗。两种分选酶锚定的表面蛋白,IsdA和IsdB,已被确定为亚单位疫苗,主动免疫后,保护实验动物免受葡萄球菌的静脉内攻击。在这里,我们调查了这种免疫的分子基础,并报告说,当被动转移到幼稚小鼠,纯化的抗体直接针对IsdA或IsdB保护对葡萄球菌脓肿形成和致命的静脉内挑战。当添加到小鼠血液中时,IsdA或IsdB特异性抗体并不能促进野生型葡萄球菌的快速调理吞噬杀伤。针对IsdA的抗体干扰血红素结合,IsdB抗体干扰这种表面蛋白结合血红蛋白的能力。由于结构基因isdA和isdB需要血红素铁清除感染的发病过程中,我们假设,IsdA和IsdB抗体可能至少部分提供保护,对葡萄球菌干扰病原体的血红素铁清除机制。
Staphylococcus aureus is the most frequent cause of bacteremia and hospital-acquired infection, however a vaccine that prevents staphylococcal disease is currently not available. Two sortase-anchored surface proteins, IsdA and IsdB, have been identified as subunit vaccines that, following active immunization, protect experimental animals against intravenous challenge with staphylococci. Here we investigate the molecular basis of this immunity and report that, when passively transferred to naïve mice, purified antibodies directed against IsdA or IsdB protected against staphylococcal abscess formation and lethal intravenous challenge. When added to mouse blood, IsdA- or IsdB-specific antibodies did not promote rapid opsonophagocytic killing of wild-type staphylococci. Antibodies directed against IsdA interfered with heme-binding and IsdB antibodies perturbed the ability of this surface protein to bind hemoglobin. As the structural genes for isdA and isdB are required for heme-iron scavenging during the pathogenesis of infection, we hypothesize that IsdA and IsdB antibodies may at least in part provide protection against staphylococci by interfering with the pathogen's heme-iron scavenging mechanisms.
DOI: 10.3201/eid1312.070629
发表时间: 2007-12
影响因子: 11.8
作者:
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影响因子: 3.6
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发表时间: 2006-07-07
影响因子: 5.6
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