The inner membrane protein YhdP modulates the rate of anterograde phospholipid flow in Escherichia coli
The inner membrane protein YhdP modulates the rate of anterograde phospholipid flow in Escherichia coli
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DOI：
10.1073/pnas.2015556117
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发表时间：
2020-10-27
影响因子：
11.1
通讯作者：
Silhavy, Thomas J.
中科院分区：
文献类型：
--
作者：
Grimm, Jacqueline;Shi, Handuo;Silhavy, Thomas J.
革兰氏阴性菌的外膜（OM）是一种选择性渗透屏障，允许吸收营养物质，同时保护细胞免受有害化合物的侵害。负责将脂多糖（LPS）、脂蛋白和β-桶蛋白转运至OM的基本途径和分子机制已被确定，但对磷脂（PL）转运知之甚少。为了鉴定能够影响PL转运的基因，我们筛选了与mlaA* 的遗传相互作用，mlaA * 是一种突变体，其中顺行PL转运导致内膜（IM）收缩并最终破裂; mlaA* 介导的裂解的表征表明PL转运可以通过高通量扩散流动机制发生。我们发现，YhdP，一种参与维持OM渗透屏障的IM蛋白，在mlaA* 介导的溶解过程中调节PL转运的速率。从mlaA* 中删除yhdP使IM运输至OM的速率降低50%，减缓IM的收缩并延迟溶解。结果，在mlaA* 介导的死亡期间，AyhdP细胞的弱化OM在IM之前进一步受损并破裂。这些研究结果表明，存在一个高通量的扩散途径PL流在大肠杆菌，是由YhdP调制。
The outer membrane (OM) of Gram-negative bacteria is a selective permeability barrier that allows uptake of nutrients while simultaneously protecting the cell from harmful compounds. The basic pathways and molecular machinery responsible for transporting lipopolysaccharides (LPS), lipoproteins, and beta-barrel proteins to the OM have been identified, but very little is known about phospholipid (PL) transport. To identify genes capable of affecting PL transport, we screened for genetic interactions with mlaA*, a mutant in which anterograde PL transport causes the inner membrane (IM) to shrink and eventually rupture; characterization of mlaA* mediated lysis suggested that PL transport can occur via a highflux diffusive flow mechanism. We found that YhdP, an IM protein involved in maintaining the OM permeability barrier, modulates the rate of PL transport during mlaA*-mediated lysis. Deletion of yhdP from mlaA* reduced the rate of IM transport to the OM by 50%, slowing shrinkage of the IM and delaying lysis. As a result, the weakened OM of AyhdP cells was further compromised and ruptured before the IM during mlaA*-mediated death. These findings demonstrate the existence of a high-flux diffusive pathway for PL flow in Escherichia coli that is modulated by YhdP.