Staphylococcus aureus protein A promotes immune suppression.
Staphylococcus aureus protein A promotes immune suppression.
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DOI：
10.1128/mbio.00764-13
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发表时间：
2013-10-01
期刊：
影响因子：
6.4
通讯作者：
DeLeo FR
中科院分区：
文献类型：
--
作者：
Kobayashi SD;DeLeo FR
金黄色葡萄球菌是世界范围内人类感染的主要原因，并且因其获得抗生素抗性的能力而臭名昭著。特别是耐甲氧西林金黄色葡萄球菌（MRSA），是医院的地方病，是美国社区相关细菌感染的最常见原因。由于严重MRSA感染的治疗选择有限，因此需要一种疫苗来保护免受此类感染。然而，最近的努力，以产生葡萄球菌疫苗在人类临床试验中取得了很小的成功。这些失败有些令人困惑，因为测试的疫苗抗原在体外促进调理吞噬作用，并在动物感染模型中提供保护。一种可能性是病原体抑制（和/或未能引发）人类保护性免疫的发展。实际上，金黄色葡萄球菌产生许多可以潜在地促进免疫逃避的分子，包括蛋白A（SpA），一种存在于细菌表面并自由分泌到细胞外环境中的免疫球蛋白（IG）结合蛋白。SpA结合抗体的Fc区和B细胞受体的Fab区，这是已知在体外阻断调理吞噬作用并导致B细胞死亡的过程。在最近的一项研究中，Falugi et al. [F. Falugi，H. K. Kim，D. M. Missiakas和O. Schneewind，mBio 4（5）：e00575-13，2013]显示，用缺乏抗体Fc-和/或Fab-结合能力的spa突变金黄色葡萄球菌菌株接种保护免受随后用USA 300流行菌株的攻击。这些发现为SpA促进体内金黄色葡萄球菌免疫逃避的想法提供了强有力的支持，并为我们开发预防严重金黄色葡萄球菌感染的疫苗的新方法奠定了基础。
Staphylococcus aureus is a prominent cause of human infections worldwide and is notorious for its ability to acquire resistance to antibiotics. Methicillin-resistant S. aureus (MRSA), in particular, is endemic in hospitals and is the most frequent cause of community-associated bacterial infections in the United States. Inasmuch as treatment options for severe MRSA infections are limited, there is need for a vaccine that protects against such infections. However, recent efforts to generate a staphylococcal vaccine have met with little success in human clinical trials. These failures are somewhat puzzling, since the vaccine antigens tested promote opsonophagocytosis in vitro and confer protection in animal infection models. One possibility is that the pathogen inhibits (and/or fails to elicit) the development of protective immunity in humans. Indeed, S. aureus produces numerous molecules that can potentially promote immune evasion, including protein A (SpA), an immunoglobulin (Ig)-binding protein present on the bacterial surface and freely secreted into the extracellular environment. SpA binds the Fc region of antibody and the Fab regions of the B-cell receptor, processes that are known to block opsonophagocytosis and cause B-cell death in vitro. In a recent study, Falugi et al. [F. Falugi, H. K. Kim, D. M. Missiakas, and O. Schneewind, mBio 4(5):e00575-13, 2013] showed that vaccination with spa mutant S. aureus strains lacking antibody Fc- and/or Fab-binding capacity protects against subsequent challenge with the USA300 epidemic strain. The findings provide strong support for the idea that SpA promotes S. aureus immune evasion in vivo and form the foundation for a new approach in our efforts to develop a vaccine that prevents severe S. aureus infections.