Key role of poly-γ-DL-glutamic acid in immune evasion and virulence of Staphylococcus epidermidis
Key role of poly-γ-DL-glutamic acid in immune evasion and virulence of Staphylococcus epidermidis
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DOI：
10.1172/jci200523523
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发表时间：
2005-03-01
影响因子：
15.9
通讯作者：
Otto, M
中科院分区：
文献类型：
--
作者：
Kocianova, S;Vuong, C;Otto, M
以表皮葡萄球菌为主的凝固酶阴性葡萄球菌是医院获得性感染的主要原因。由于生物被膜的形成和频繁的抗生素耐药性，治疗尤其困难。然而，这些重要的条件致病菌的毒力机制仍然没有得到很好的描述。在这里，我们证明，表皮葡萄球菌分泌聚γ-DL-谷氨酸(PGA)，以促进人类宿主的生长和生存。重要的是，PGA有效地保护表皮葡萄球菌免受天然宿主防御的关键成分，即抗菌肽和中性粒细胞吞噬，并且对于设备相关感染的持久性是不可或缺的。此外，PGA保护表皮葡萄球菌免受高盐浓度的影响，这是其自然环境的一个关键特征，！人的皮肤。值得注意的是，PGA是由所有被测试的表皮葡萄球菌和一系列密切相关的凝固酶阴性葡萄球菌合成的，其中大多数是条件致病菌。我们的研究提出了PGA的重要的：新的生物学功能，并表明PGA是治疗由表皮葡萄球菌和相关葡萄球菌引起的疾病的良好靶点。
Coagulase-negative staphylococci, with the leading species Stapbylococcus epidermidis, are the predominant cause of hospital-acquired infections. Treatment is especially difficult owing to biofilm formation and frequent antibiotic resistance. However, virulence mechanisms of these important opportunistic pathogens have remained poorly characterized. Here we demonstrate that S. epidermidis secretes poly-gamma-DL-glutamic acid (PGA) to facilitate growth and survival in the human host. Importantly, PGA efficiently sheltered S. epidermidis from key components of innate host defense, namely antimicrobial peptides and neutrophil phagocytosis, and was indispensable for persistence during device-related infection. Furthermore, PGA protected S. epidermidis from high salt concentration, a key feature of its natural environment, the! human skin. Notably, PGA was synthesized by all tested strains of S. epidermidis and a series of closely related coagulase-negative staphylococci, most of which are opportunistic pathogens. Our study presents important: novel biological functions for PGA and indicates that PGA represents an excellent target for therapeutic maneuvers aimed at treating disease caused by S. epidermidis and related staphylococci.