Department of Microbiology, Cornell University, Ithaca, New York 14853-8101 14853-8101, USA.
J Bacteriol. 2011 Oct;193(20):5793-801. doi: 10.1128/JB.05862-11. Epub 2011 Aug 19.
The transglycosylation step of cell wall synthesis is a prime antibiotic target because it is essential and specific to bacteria. Two antibiotics, ramoplanin and moenomycin, target this step by binding to the substrate lipid II and the transglycosylase enzyme, respectively. Here, we compare the ramoplanin and moenomycin stimulons in the Gram-positive model organism Bacillus subtilis. Ramoplanin strongly induces the LiaRS two-component regulatory system, while moenomycin almost exclusively induces genes that are part of the regulon of the extracytoplasmic function (ECF) σ factor σ(M). Ramoplanin additionally induces the ytrABCDEF and ywoBCD operons, which are not part of a previously characterized antibiotic-responsive regulon. Cluster analysis reveals that these two operons are selectively induced by a subset of cell wall antibiotics that inhibit lipid II function or recycling. Repression of both operons requires YtrA, which recognizes an inverted repeat in front of its own operon and in front of ywoB. These results suggest that YtrA is an additional regulator of cell envelope stress responses.
细胞壁合成的转糖基化步骤是抗生素的主要靶标，因为它对细菌是必需且特异的。两种抗生素，雷莫拉宁和莫能菌素，分别通过与底物脂质 II 和转糖基化酶结合来靶向该步骤。在这里，我们比较了革兰氏阳性模式生物枯草芽孢杆菌中雷莫拉宁和莫能菌素的刺激物。雷莫拉宁强烈诱导 LiaRS 双组分调节系统，而莫能菌素几乎只诱导细胞外功能 (ECF)σ 因子 σ(M) 调节子的基因。雷莫拉宁还诱导 ytrABCDEF 和 ywoBCD 操纵子，这些操纵子不属于以前表征的抗生素响应调节子。聚类分析表明，这两个操纵子被一组抑制脂质 II 功能或循环的细胞壁抗生素选择性诱导。这两个操纵子的抑制都需要 YtrA，它识别自身操纵子和 ywoB 前面的反向重复。这些结果表明，YtrA 是细胞包膜应激反应的另一个调节剂。
