Cell wall stress responses in Bacillus subtilis:: the regulatory network of the bacitracin stimulon
Cell wall stress responses in Bacillus subtilis:: the regulatory network of the bacitracin stimulon
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DOI：
10.1046/j.1365-2958.2003.03786.x
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发表时间：
2003-12-01
影响因子：
3.6
通讯作者：
Helmann, JD
中科院分区：
文献类型：
--
作者：
Mascher, T;Margulis, NG;Helmann, JD
为了应对亚致死浓度的抗生素，细菌通常会诱发适应性反应，从而导致抗生素耐药性。我们报告了枯草芽孢杆菌对杆菌肽的反应，杆菌肽是一种在自然环境中发现的细胞壁生物合成抑制剂。对杆菌肽处理细胞的整体转录谱的分析揭示了由两个替代 sigma 因子（sigma(B) 和 sigma(M)）和三个双组分系统（YvqEC、YvcPQ 和 BceRS）协调的反应。所有三个双组分系统都位于杆菌肽强烈诱导的靶基因旁边，相应的组氨酸激酶具有不寻常的拓扑结构：它们的细胞外传感结构域缺乏约 100 个氨基酸，几乎完全埋在细胞质膜中。序列分析表明，这种新型 N 末端传感结构域是组氨酸激酶亚家族的一个特征，几乎完全存在于革兰氏阳性菌中，并且经常与 ABC 转运蛋白相关。对杆菌肽诱导基因的系统突变分析导致鉴定出新的杆菌肽抗性决定簇 bceAB，其编码假定的 ABC 转运蛋白。 bcrC杆菌肽抗性基因受sigma(X)和sigma(M)双重控制，也被杆菌肽诱导。通过比较杆菌肽和万古霉素刺激物，我们可以区分杆菌肽特异性诱导的基因座和由多种细胞壁活性抗生素诱导的基因座。
In response to sublethal concentrations of antibiotics, bacteria often induce an adaptive response that can contribute to antibiotic resistance. We report the response of Bacillus subtilis to bacitracin, an inhibitor of cell wall biosynthesis found in its natural environment. Analysis of the global transcriptional profile of bacitracin-treated cells reveals a response orchestrated by two alternative sigma factors (sigma(B) and sigma(M)) and three two-component systems (YvqEC, YvcPQ and BceRS). All three two-component systems are located next to target genes that are strongly induced by bacitracin, and the corresponding histidine kinases share an unusual topology: they lack about 100 amino acids in their extracellular sensing domain, which is almost entirely buried in the cytoplasmic membrane. Sequence analysis indicates that this novel N-terminal sensing domain is a characteristic feature of a subfamily of histidine kinases, found almost entirely in Gram-positive bacteria and frequently linked to ABC transporters. A systematic mutational analysis of bacitracin-induced genes led to the identification of a new bacitracin-resistance determinant, bceAB, encoding a putative ABC transporter. The bcrC bacitracin resistance gene, which is under the dual control of sigma(X) and sigma(M), was also induced by bacitracin. By comparing the bacitracin and the vancomycin stimulons, we can differentiate between loci induced specifically by bacitracin and those that are induced by multiple cell wall-active antibiotics.