The mammalian ionic environment dictates microbial susceptibility to antimicrobial defense peptides
The mammalian ionic environment dictates microbial susceptibility to antimicrobial defense peptides
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DOI：
10.1096/fj.05-4406com
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发表时间：
2006-01-01
期刊：
影响因子：
4.8
通讯作者：
Gallo, RL
中科院分区：
文献类型：
--
作者：
Dorschner, RA;Lopez-Garcia, B;Gallo, RL
抗菌肽（AMP）已在动物和人体系统中被证明是有效的天然抗生素。然而，尚不清楚它们如何提供保护；当在合成抗生素的培养条件下进行分析时，它们通常表现出无活性。这种失活与生理浓度的氯化钠或血清的功能丧失有关。在这项研究中，我们表明宿主离子条件的平衡决定了微生物对 AMP 的敏感性。碳酸盐被认为是哺乳动物组织中存在的关键离子因子，它赋予 AMP（例如抗菌肽和防御素）在生理 NaCl 浓度下杀死细菌的能力。在适应含碳酸盐溶液后，尽管生长速度没有变化，但金黄色葡萄球菌和大肠杆菌的结构和基因表达发生了整体变化。我们的研究结果表明，细胞壁厚度和 Sigma 因子 B 表达的变化与 AMP LL-37 敏感性的增加相对应。这些观察结果为涉及先天免疫效应分子功能的因素提供了新的见解，并表明新抗菌药物的发现应专门针对宿主中存在的病原体，而不是培养液中生长的细菌的明显不同表型。-Dorschner, R. A.、Lopez-Garcia, B.、Peschel, A.、Kraus, D.、Morikawa, K.、Nizet, V.、Gallo, R. L. 哺乳动物离子环境决定微生物对抗菌防御肽的敏感性。
Antimicrobial peptides (AMPs) have been shown in animal and human systems to be effective natural antibiotics. However, it is unclear how they convey protection; they often appear inactive when assayed under culture conditions applied to synthetic antibiotics. This inactivation has been associated with loss of function in physiological concentrations of NaCl or serum. In this study we show that the balance of host ionic conditions dictate microbial sensitivity to AMPs. Carbonate is identified as the critical ionic factor present in mammalian tissues that imparts the ability of AMPs such as cathelicidins and defensins to kill at physiological NaCl concentrations. After adapting to carbonate-containing solutions, global changes occur in Staphylococcus aureus and Escherichia coli structure and gene expression despite no change in growth rate. Our findings show that changes in cell wall thickness and Sigma factor B expression correspond to the increased susceptibility to the AMP LL-37. These observations provide new insight into the factors involved in enabling function of innate immune effector molecules, and suggest that discovery of new antimicrobials should specifically target pathogens as they exist in the host and not the distinctly different phenotype of bacteria grown in culture broth.-Dorschner, R. A., Lopez-Garcia, B., Peschel, A., Kraus, D., Morikawa, K., Nizet, V., Gallo, R. L. The mammalian ionic environment dictates microbial susceptibility to antimicrobial defense peptides.