Redefining the essential trafficking pathway for outer membrane lipoproteins
Redefining the essential trafficking pathway for outer membrane lipoproteins
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DOI：
10.1073/pnas.1702248114
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发表时间：
2017-05-02
影响因子：
11.1
通讯作者：
Silhavy, Thomas J.
中科院分区：
文献类型：
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作者：
Grabowicz, Marcin;Silhavy, Thomas J.
革兰氏阴性菌的外膜是一种通透性屏障，是一种内在的抗生素耐药因子。脂蛋白是一种OM组分，在细胞壁合成、多种分泌系统和抗生素外排泵中发挥作用。此外，组装屏障的每一台基本OM机器都需要一种或多种脂蛋白。这种依赖性被认为解释了周质伴侣LOLA及其OM受体LOLB将脂蛋白输送到OM的重要性。然而，我们表明，在缺乏底物的菌株中，错误定位时是有毒的，LOLA和LOLB都可以通过激活包膜应激反应而完全绕过，而不会影响基本脂蛋白的运输。我们认为CPX应激反应是脂蛋白运输的监控器，其任务是保护细胞免受错误定位的脂蛋白的影响。此外，我们的发现表明，在某些条件下，存在一条替代的运输途径，可以绕过LOLA和LOLB的功能，这意味着这些蛋白质在脂蛋白运输中不执行任何真正必要的机械性步骤。相反，这些蛋白质的关键功能是防止错误定位的脂蛋白的致命积累。
The outer membrane (OM) of Gram-negative bacteria is a permeability barrier and an intrinsic antibiotic resistance factor. Lipoproteins are OM components that function in cell wall synthesis, diverse secretion systems, and antibiotic efflux pumps. Moreover, each of the essential OM machines that assemble the barrier requires one or more lipoproteins. This dependence is thought to explain the essentiality of the periplasmic chaperone LolA and its OM receptor LolB that traffic lipoproteins to the OM. However, we show that in strains lacking substrates that are toxic when mislocalized, both LolA and LolB can be completely bypassed by activating an envelope stress response without compromising trafficking of essential lipoproteins. We identify the Cpx stress response as a monitor of lipoprotein trafficking tasked with protecting the cell from mislocalized lipoproteins. Moreover, our findings reveal that an alternate trafficking pathway exists that can, under certain conditions, bypass the functions of LolA and LolB, implying that these proteins do not perform any truly essential mechanistic steps in lipoprotein trafficking. Instead, these proteins' key function is to prevent lethal accumulation of mislocalized lipoproteins.