The CpxR/CpxA Two-component System Up-regulates Two Tat-dependent Peptidoglycan Amidases to Confer Bacterial Resistance to Antimicrobial Peptide
The CpxR/CpxA Two-component System Up-regulates Two Tat-dependent Peptidoglycan Amidases to Confer Bacterial Resistance to Antimicrobial Peptide
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DOI：
10.1074/jbc.m110.200352
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发表时间：
2011-02-18
影响因子：
4.8
通讯作者：
Shi, Yixin
中科院分区：
文献类型：
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作者：
Weatherspoon-Griffin, Natasha;Zhao, Guang;Shi, Yixin
我们证明了双精氨酸易位（Tat）系统有助于细菌对阳离子抗菌肽（camp）的耐药性。我们的研究结果表明，编码Tat复合物亚基的tatC基因的缺失导致沙门氏菌和大肠杆菌对鱼精蛋白敏感。我们筛选了编码已知和预测tau依赖蛋白的染色体位点，发现由amiA和amiC编码的两个n -乙酰muramyl - l-丙氨酸氨基酶，提高了细菌对鱼精蛋白和α -螺旋肽magainin 2和melittin的抗性，但对β -sheet防御蛋白HNP-1和脂肽多粘菌素b的抗性，遗传学分析表明，当nlpE过表达时，沙门氏菌中amiA和amiC位点的转录都被CpxR/CpxA双组份系统上调。足迹分析表明，CpxR蛋白可以与amiA和amiC启动子在CpxR盒子上相互作用，CpxR盒子位于预测的-10和-35区域之间，但存在于这两个基因的不同链上。此外，我们的研究结果表明，CpxR/CpxA系统的激活可以促进鱼精蛋白抗性，因为nlpE过表达会提高野生型菌株的这种抗性，而CpxR缺失突变体则不会。因此，我们发现了一种新的转录调控途径，其中Cpx包膜应激反应系统通过控制肽聚糖酰胺酶活性来部分调节细胞包膜的完整性，从而赋予细菌对鱼精蛋白和α -螺旋camp的抗性。我们的研究对理解肽聚糖代谢的转录调控具有重要意义，也为细菌包膜在CAMP耐药中的作用提供了新的见解。
We demonstrate that the twin arginine translocation (Tat) system contributes to bacterial resistance to cationic antimicrobial peptides (CAMPs). Our results show that a deletion at the tatC gene, which encodes a subunit of the Tat complex, caused Salmonella and Escherichia coli to become susceptible to protamine. We screened chromosomal loci that encode known and predicted Tat-dependent proteins and found that two N-acetylmuramoyl-L-alanine amidases, encoded by amiA and amiC, elevated bacterial resistance to protamine and alpha-helical peptides magainin 2 and melittin but not to beta-sheet defensin HNP-1 and lipopeptide polymyxin B. Genetic analysis suggests that transcription of both amiA and amiC loci in Salmonella is up-regulated by the CpxR/CpxA two-component system when nlpE is overexpressed. A footprinting analysis reveals that CpxR protein can interact with amiA and amiC promoters at the CpxR box, which is localized between the predicted -10 and -35 regions but present on different strands in these two genes. In addition, our results show that activation of the CpxR/CpxA system can facilitate protamine resistance because nlpE overexpression elevates this resistance in the wild-type strain but not the cpxR deletion mutant. Thus, we uncover a new transcriptional regulation pathway in which the Cpx envelope stress response system modulates the integrity of the cell envelope in part by controlling peptidoglycan amidase activity, which confers bacterial resistance to protamine and alpha-helical CAMPs. Our studies have important implications for understanding transcriptional regulation of peptidoglycan metabolism and also provide new insights into the role of the bacterial envelope in CAMP resistance.