Complement c5a generation by staphylococcal biofilms.
Complement c5a generation by staphylococcal biofilms.
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DOI：
10.1097/shk.0b013e31828d9324
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发表时间：
2013-04
期刊：
影响因子：
--
通讯作者：
Younger JG
中科院分区：
文献类型：
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作者：
Satorius AE;Szafranski J;Pyne D;Ganesan M;Solomon MJ;Newton DW;Bortz DM;Younger JG
生物膜的产生是复苏和重症监护中使用的导管和其他医疗器械医院感染的一个核心特征。然而，非常有效的生物膜形成病原体表皮葡萄球菌通常会产生适度的宿主炎症反应，并且几乎不会产生与毒性更强的病原体相关的体征和症状。为了研究细菌生物膜形成对激发先天免疫反应的影响，我们研究了人血清在接触表皮葡萄球菌生物膜后对主要补体过敏毒素 C5a 的加工。研究了野生型表皮葡萄球菌以及 sarA（一种促进生物膜形成多糖细胞间粘附素 PIA 合成的调节蛋白）和 icaB（负责 PIA 的出口后加工）的突变体。 C5a 的释放量是暴露生物膜表面积的函数，约为 1 fmol cm−2 sec−1，并且取决于 PIA 的存在。实验结果被用来为受感染的中心静脉导管释放 C5a 的基于生理学的药代动力学模型提供信息，这是表皮葡萄球菌引起人类疾病的主要途径之一。这些模拟表明，完全被表皮葡萄球菌覆盖的上腔静脉导管上的 C5a 释放量将低于警报循环白细胞所需的量。结合起来，实验和计算结果与临床观察高度一致，其中与这种重要病原体相关的中心静脉相关血流感染的临床症状通常是减弱的。
Biofilms production is a central feature of nosocomial infection of catheters and other medical devices used in resuscitation and critical care. However, the very effective biofilm forming pathogen Staphylococcus epidermidis often produces a modest host inflammatory response and few of the signs and symptoms associated with more virulent pathogens. To examine the impact of bacterial biofilm formation on provocation of an innate immune response, we studied the elaboration of the major complement anaphylatoxin C5a by human serum upon contact with S. epidermidis biofilms. Wildtype S. epidermidis and mutants of sarA (a regulatory protein that promotes synthesis of the biofilm-forming polysaccharide intercellular adhesin, PIA) and icaB (responsible for post-export processing of PIA) were studied. C5a release, as a function of exposed biofilm surface area, was on the order of 1 fmol cm−2 sec−1 and was dependent on the presence of PIA. Experimental results were used to inform a physiologically-based pharmacokinetic model of C5a release by an infected central venous catheter, one of S. epidermidis' primary means of causing human disease. These simulations revealed that the magnitude of C5a release on a superior vena cava catheter completely covered with S. epidermidis would be lower than necessary to alert circulating leukocytes. Combined, the experimental and computational results are highly consistent with clinical observations in which the clinical signs of central line associated bloodstream infection are often muted in association with this important pathogen.