Gram-positive three-component antimicrobial peptide-sensing system
Gram-positive three-component antimicrobial peptide-sensing system
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DOI：
10.1073/pnas.0702159104
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发表时间：
2007-05-29
影响因子：
11.1
通讯作者：
Otto, Michael
中科院分区：
文献类型：
--
作者：
Li, Min;Lai, Yuping;Otto, Michael
为了在人体定植或感染期间存活，微生物必须绕过先天宿主防御机制。抗菌肽代表了宿主先天防御的关键组成部分，特别是在吞噬细胞和上皮表面上。然而，尚不清楚临床上重要的革兰氏阳性菌群如何感知抗微生物肽以协调定向防御反应。通过确定医院病原体表皮葡萄球菌中对人P-防御素3的全基因组基因调节反应，我们发现了一种控制主要特异性耐药性的抗菌肽传感器系统！革兰氏阳性菌的作用机制，与革兰氏阴性菌PhoP/PhoQ系统无关。它包含一个经典的双组分信号转导蛋白和一个不寻常的第三蛋白，所有这些都是信号转导和抗菌肽抗性不可或缺的。此外，我们的数据表明，传感器蛋白中具有高密度负电荷的非常短的细胞外环负责抗菌肽结合和观察到的阳离子抗菌肽的特异性。我们的研究表明，革兰氏阳性菌已经开发出一种有效和独特的方式来控制抗菌肽的耐药机制，这可能为抗菌药物的开发提供一个有前途的目标。
To survive during colonization or infection of the human body, microorganisms must circumvent mechanisms of innate host defense. Antimicrobial peptides represent a key component of innate host defense, especially in phagocytes and on epithelial Surfaces. However, it is not known how the clinically important group of Gram-positive bacteria sense antimicrobial peptides to coordinate a directed defensive response. By determining the genome-wide gene regulatory response to human P-defensin 3 in the nosocomial pathogen Staphylococcus epidermidis, we discovered an antimicrobial peptide sensor system that controls major specific resistance! mechanisms of Gram-positive bacteria and is unrelated to the Gram-negative PhoP/PhoQ system. It contains a classical two-component signal transducer and an unusual third protein, all of which are indispensable for signal transduction and antimicrobial peptide resistance. Furthermore, our data indicate that a very short, extracellular loop with a high density of negative charges in the sensor protein is responsible for antimicrobial peptide binding and the observed specificity for cationic antimicrobial peptides. Our study shows that Gram-positive bacteria have developed an efficient and unique way of controlling resistance mechanisms to antimicrobial peptides, which may provide a promising target for antimicrobial drug development.