Delivery of Cardiolipins to the Salmonella Outer Membrane Is Necessary for Survival within Host Tissues and Virulence
Delivery of Cardiolipins to the Salmonella Outer Membrane Is Necessary for Survival within Host Tissues and Virulence
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DOI：
10.1016/j.chom.2015.03.003
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发表时间：
2015-04-08
影响因子：
30.3
通讯作者：
Miller, Samuel I.
中科院分区：
文献类型：
--
作者：
Dalebroux, Zachary D.;Edrozo, Mauna B.;Miller, Samuel I.
革兰氏阴性菌的外膜（OM）是一种不对称的脂质双层，作为环境的屏障。在感染期间，革兰氏阴性菌重塑其OM以促进宿主组织内的存活和复制。沙门氏菌依赖于PhoPQ双组分调节剂来协调OM重塑以响应环境线索。在筛选鼠伤寒沙门氏菌中PhoPQ调节OM重塑的介质时，我们确定了PbgA，一种含有周质结构域的跨膜蛋白，其结合内膜附近的心磷脂甘油磷脂并促进其PhoPQ调节的向OM的运输。纯化的PbgA寡聚体是四聚体，并且周质结构域包含以PhoPQ依赖性方式结合OM的球状区域。因此，PbgA形成复合物，其可以桥接包膜以调节心磷脂递送。PbgA球状区域缺失突变细菌的发病机制严重衰减，这表明增加心磷脂贩运到OM是必要的沙门氏菌在宿主组织内激活PhoPQ生存。
The outer membrane (OM) of Gram-negative bacteria is an asymmetric lipid bilayer that serves as a barrier to the environment. During infection, Gram-negative bacteria remodel their OM to promote survival and replication within host tissues. Salmonella rely on the PhoPQ two-component regulators to coordinate OM remodeling in response to environmental cues. In a screen for mediators of PhoPQ-regulated OM remodeling in Salmonella Typhimurium, we identified PbgA, a periplasmic domain-containing transmembrane protein, which binds cardiolipin glycerophospholipids near the inner membrane and promotes their PhoPQ-regulated trafficking to the OM. Purified-PbgA oligomers are tetrameric, and the periplasmic domain contains a globular region that binds to the OM in a PhoPQ-dependent manner. Thus, PbgA forms a complex that may bridge the envelope for regulated cardiolipin delivery. PbgA globular region-deleted mutant bacteria are severely attenuated for pathogenesis, suggesting that increased cardiolipin trafficking to the OM is necessary for Salmonella to survive within host tissues that activate PhoPQ.