Laboratoire de Microbiologie et Génétique Moléculaires (LMGM), Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPS, Toulouse, France.
Synthetic Biology Group, Microbiology Department, Institut Pasteur, Paris, France.
Elife. 2021 Apr 13;10:e67817. doi: 10.7554/eLife.67817.
In Proteobacteria, integral outer membrane proteins (OMPs) are crucial for the maintenance of the envelope permeability barrier to some antibiotics and detergents. In Enterobacteria, envelope stress caused by unfolded OMPs activates the sigmaE (σ) transcriptional response. σ upregulates OMP biogenesis factors, including the β-barrel assembly machinery (BAM) that catalyses OMP folding. Here we report that DolP (formerly YraP), a σ-upregulated and poorly understood outer membrane lipoprotein, is crucial for fitness in cells that undergo envelope stress. We demonstrate that DolP interacts with the BAM complex by associating with outer membrane-assembled BamA. We provide evidence that DolP is important for proper folding of BamA that overaccumulates in the outer membrane, thus supporting OMP biogenesis and envelope integrity. Notably, mid-cell recruitment of DolP had been linked to regulation of septal peptidoglycan remodelling by an unknown mechanism. We now reveal that, during envelope stress, DolP loses its association with the mid-cell, thereby suggesting a mechanistic link between envelope stress caused by impaired OMP biogenesis and the regulation of a late step of cell division.
在变形菌门中，完整的外膜蛋白（OMP）对于维持某些抗生素和去污剂对包膜的通透性屏障至关重要。在肠杆菌科中，未折叠的 OMP 引起的包膜应激会激活 σE（σ）转录反应。σ上调 OMP 生物发生因子，包括催化 OMP 折叠的β桶组装机制（BAM）。在这里，我们报告说，DolP（以前称为 YraP），一种 σ 上调且知之甚少的外膜脂蛋白，对于经历包膜应激的细胞的适应性至关重要。我们证明 DolP 通过与在外膜组装的 BamA 结合与 BAM 复合物相互作用。我们提供的证据表明，DolP 对于 BamA 的正确折叠很重要，BamA 在 OMP 生物发生和包膜完整性方面过度积累。值得注意的是，DolP 的中芯募集与未知机制调节隔膜肽聚糖重塑有关。我们现在揭示，在包膜应激期间，DolP 失去了与中芯的关联，从而表明由于 OMP 生物发生受损而导致的包膜应激与细胞分裂后期步骤的调节之间存在机制联系。
