The role of the essential GTPase ObgE in regulating lipopolysaccharide synthesis in Escherichia coli

During growth, cells need to synthesize and expand their envelope, a process that requires careful regulation. Here, we show that the GTPase ObgE of E. coli contributes to the regulation of lipopolysaccharide (LPS) synthesis, an essential component of the Gram-negative outer membrane. Using a dominant-negative mutant (named ObgE*), we show a direct interaction between ObgE and LpxA, which catalyzes the first step in LPS synthesis. This interaction is enhanced by the mutation in ObgE* which, when bound to GTP, leads to inhibition of LpxA, decreased LPS synthesis, and cell death. Although wild-type ObgE does not exert the same strong effects as ObgE* on LpxA or LPS synthesis, our data indicate that ObgE participates in the regulation of cell envelope synthesis in E. coli. Because ObgE also influences other cellular functions (i.e., ribosome assembly, DNA replication, etc.), it seems increasingly plausible that this GTPase coordinates several processes to finetune cell growth.

细胞在生长过程中需合成并扩张其包膜，该过程依赖精密的调控机制。本研究证实，大肠杆菌（E. coli）的GTP酶（GTPase）ObgE参与调控脂多糖（lipopolysaccharide, LPS）的合成——脂多糖是革兰氏阴性（Gram-negative）菌外膜的核心组成成分。我们通过一种命名为ObgE*的显性负突变体（dominant-negative mutant）实验，证明ObgE与催化脂多糖合成第一步的酶LpxA存在直接相互作用。ObgE*携带的突变可增强该相互作用；当ObgE*结合GTP时，会抑制LpxA的活性，进而导致脂多糖合成减少并引发细胞死亡。尽管野生型ObgE对LpxA活性或脂多糖合成的调控强度不及ObgE*，但我们的实验数据表明，ObgE确实参与了大肠杆菌细胞包膜合成的调控过程。鉴于ObgE还可影响其他细胞功能（如核糖体组装、DNA复制等），这种GTP酶能够协调多种生理过程以微调细胞生长的假说愈发可信。