YhdP, TamB, and YdbH Are Redundant but Essential for Growth and Lipid Homeostasis of the Gram-Negative Outer Membrane.
YhdP, TamB, and YdbH Are Redundant but Essential for Growth and Lipid Homeostasis of the Gram-Negative Outer Membrane.
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DOI：
10.1128/mbio.02714-21
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发表时间：
2021-12-21
期刊：
影响因子：
6.4
通讯作者：
Kumar S
中科院分区：
文献类型：
--
作者：
Ruiz N;Davis RM;Kumar S
细菌的细胞膜是与环境和其他生物接触的第一道防线和接触点。因此，包膜生物发生对细菌的生存和生理至关重要，经常成为抗菌剂的靶标。革兰氏阴性菌有一个多层的包膜，由内膜和外膜(分别为IM和OM)分隔。OM是许多抗菌剂的屏障，因为它的不对称脂类结构，磷脂组成内叶，脂多糖(LPS)组成外叶。由于脂质合成发生在IM，磷脂和脂多糖在生长过程中穿过细胞膜并不对称地组装在OM处。磷脂是如何转运到OM的，目前尚不清楚。最近，大肠杆菌蛋白YhdP被提出通过一种未知的机制参与这一过程。YhdP属于ASMA样家族，含有与脂类转运蛋白同源的结构域。在这里，我们使用遗传学来研究大肠杆菌中ASMA样蛋白家族的六个成员。我们的数据表明，YhdP及其类似的TAMB和YDBH在执行细胞被膜中的基本功能方面是冗余的，但不是等价的。在类似ASMA的对虾中，只有YhdP、TAMB和YDBH的联合丢失是致命的，并且这三种蛋白质中的任何一种都足以生长。我们还证明了这些蛋白是OM脂质平衡所必需的，并提出它们是OM生物发生所需的长期追逐的磷脂转运体。
The bacterial cell envelope is the first line of defense and point of contact with the environment and other organisms. Envelope biogenesis is therefore crucial for the survival and physiology of bacteria and is often targeted by antimicrobials. Gram-negative bacteria have a multilayered envelope delimited by an inner and outer membrane (IM and OM, respectively). The OM is a barrier against many antimicrobials because of its asymmetric lipid structure, with phospholipids composing the inner leaflet and lipopolysaccharides (LPS) the outer leaflet. Since lipid synthesis occurs at the IM, phospholipids and LPS are transported across the cell envelope and asymmetrically assembled at the OM during growth. How phospholipids are transported to the OM remains unknown. Recently, the Escherichia coli protein YhdP has been proposed to participate in this process through an unknown mechanism. YhdP belongs to the AsmA-like clan and contains domains homologous to those found in lipid transporters. Here, we used genetics to investigate the six members of the AsmA-like clan of proteins in E. coli. Our data show that YhdP and its paralogs TamB and YdbH are redundant, but not equivalent, in performing an essential function in the cell envelope. Among the AsmA-like paralogs, only the combined loss of YhdP, TamB, and YdbH is lethal, and any of these three proteins is sufficient for growth. We also show that these proteins are required for OM lipid homeostasis and propose that they are the long-sought-after phospholipid transporters that are required for OM biogenesis.