Anatomy of the bacitracin resistance network in Bacillus subtilis
Anatomy of the bacitracin resistance network in Bacillus subtilis
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DOI：
10.1111/mmi.13336
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发表时间：
2016-05-01
影响因子：
3.6
通讯作者：
Fritz, Georg
中科院分区：
文献类型：
--
作者：
Radeck, Jara;Gebhard, Susanne;Fritz, Georg
对抗菌肽（amp）的保护通常涉及多个并行生产，具有良好特征的耐药决定因素。到目前为止，人们对这些抗性模块如何相互作用以及它们如何共同保护细胞知之甚少。在这里，我们研究了枯草芽孢杆菌在受到抑制脂质II周期的AMP杆菌肽刺激时，不同包膜层间的相互依赖性。潜在的调控网络协调了ABC转运体BceAB、UPP磷酸酶BcrC和噬菌体休克蛋白LiaIH的产生。我们的系统级分析揭示了一个清晰的层次结构，使我们能够区分杆菌肽耐药的初级（BceAB）和次级（BcrC和LiaIH）层。删除初级层会引起二级层的增强诱导，以部分补偿这种损失。本研究揭示了LiaIH在杆菌肽耐药性中的直接作用，为Lia系统的反馈调节提供了新的见解，并证明了BcrC在维持细胞壁稳态中的关键作用。杆菌肽网络中的代偿调节也可以解释基因表达噪声如何在抗性层之间传播。我们认为枯草芽孢杆菌杆菌素耐药网络中的这种主动冗余是许多细菌抗生素耐药网络中发现的一般原则。
Protection against antimicrobial peptides (AMPs) often involves the parallel production of multiple, well-characterized resistance determinants. So far, little is known about how these resistance modules interact and how they jointly protect the cell. Here, we studied the interdependence between different layers of the envelope stress response of Bacillus subtilis when challenged with the lipid II cycle-inhibiting AMP bacitracin. The underlying regulatory network orchestrates the production of the ABC transporter BceAB, the UPP phosphatase BcrC and the phage-shock proteins LiaIH. Our systems-level analysis reveals a clear hierarchy, allowing us to discriminate between primary (BceAB) and secondary (BcrC and LiaIH) layers of bacitracin resistance. Deleting the primary layer provokes an enhanced induction of the secondary layer to partially compensate for this loss. This study reveals a direct role of LiaIH in bacitracin resistance, provides novel insights into the feedback regulation of the Lia system, and demonstrates a pivotal role of BcrC in maintaining cell wall homeostasis. The compensatory regulation within the bacitracin network can also explain how gene expression noise propagates between resistance layers. We suggest that this active redundancy in the bacitracin resistance network of B. subtilis is a general principle to be found in many bacterial antibiotic resistance networks.