PlsX 和 PlsY:革兰氏阴性细菌中甘油磷脂合成以外的其他作用。

IF 5.1 1区 生物学 Q1 MICROBIOLOGY
mBio Pub Date : 2024-10-30 DOI:10.1128/mbio.02969-24
Audrey N Rex, Brent W Simpson, Gregory Bokinsky, M Stephen Trent
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引用次数: 0

摘要

革兰氏阴性菌的外膜具有独特的不对称性,内叶为甘油磷脂(GPL),外叶为脂多糖(LPS)。因此,必须严格控制 GPL 和 LPS 的合成,以保持这一重要结构的完整性。我们试图破解为什么像大肠杆菌这样的生物拥有两条冗余途径--PlsB 和 PlsX/Y--来合成 GPL 前体溶血磷脂酸(LPA)。LPA 然后由 PlsC 转化为 GPL 合成的通用前体--磷脂酸(PA)。PlsB 和 PlsC 在大肠杆菌中至关重要,表明它们是 PA 合成的主要途径。虽然 PlsX 或 PlsY 的单独缺失对细胞影响不大,但两者的缺失都是致命的。为了了解这种看似多余的 PlsX/Y 通路的合成致死性,我们进行了抑制因子筛选。抑制因子分析表明,∆plsXY 需要增加 GPL 前体甘油-3-磷酸(G3P)的水平。同样,∆plsXY 需要补充 G3P 才能存活。此外,PlsX 的缺失使脂肪酸合成失调,导致长链脂肪酸增加。我们的研究表明,尽管 PlsX/Y 共同促进了 PA 的合成,但它们也有助于调节整个膜的生物生成。因此,∆plsXY 的合成致死率是多因素的,这表明 PlsX/Y 一直作为一个冗余系统维持着,以微调主要脂质的合成并促进细胞膜的平衡。重要意义革兰氏阴性细菌必须在细胞膜内保持甘油磷脂和脂多糖的最佳比例才能存活。维持适当的外膜不对称性可提高对毒素和抗生素的抵抗力。在这里,我们描述了 PlsX 和 PlsY 在大肠杆菌中除了合成溶血磷脂酸(所有甘油磷脂的关键前体)之外的其他作用。这些发现表明,PlsX 和 PlsY 还在影响脂质合成的平衡方面发挥着更大的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
PlsX and PlsY: Additional roles beyond glycerophospholipid synthesis in Gram-negative bacteria.

The unique asymmetry of the Gram-negative outer membrane, with glycerophospholipids (GPLs) in the inner leaflet and lipopolysaccharide (LPS) in the outer leaflet, works to resist external stressors and prevent the entry of toxic compounds. Thus, GPL and LPS synthesis must be tightly controlled to maintain the integrity of this essential structure. We sought to decipher why organisms like Escherichia coli possess two redundant pathways-PlsB and PlsX/Y-for synthesis of the GPL precursor lysophosphatidic acid (LPA). LPA is then converted by PlsC to the universal precursor for GPL synthesis, phosphatidic acid (PA). PlsB and PlsC are essential in E. coli, indicating they serve as the major pathway for PA synthesis. While loss of PlsX or PlsY individually has little consequence on the cell, the absence of both was lethal. To understand the synthetic lethality of this seemingly redundant PlsX/Y pathway, we performed a suppressor screen. Suppressor analysis indicated that ∆plsXY requires increased levels of glycerol-3-phosphate (G3P), a GPL precursor. In agreement, ∆plsXY required supplementation with G3P for survival. Furthermore, loss of PlsX dysregulated fatty acid synthesis, resulting in increased long-chain fatty acids. We show that although PlsX/Y together contribute to PA synthesis, they also contribute to the regulation of overall membrane biogenesis. Thus, synthetic lethality of ∆plsXY is multifactorial, suggesting that PlsX/Y has been maintained as a redundant system to fine-tune the synthesis of major lipids and promote cell envelope homeostasis.IMPORTANCEGram-negative bacteria must maintain optimal ratios of glycerophospholipids and lipopolysaccharide within the cell envelope for viability. Maintenance of proper outer membrane asymmetry allows for resistance to toxins and antibiotics. Here, we describe additional roles of PlsX and PlsY in Escherichia coli beyond lysophosphatidic acid synthesis, a key precursor of all glycerophospholipids. These findings suggest that PlsX and PlsY also play a larger role in impacting homeostasis of lipid synthesis.

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来源期刊
mBio
mBio MICROBIOLOGY-
CiteScore
10.50
自引率
3.10%
发文量
762
审稿时长
1 months
期刊介绍: mBio® is ASM''s first broad-scope, online-only, open access journal. mBio offers streamlined review and publication of the best research in microbiology and allied fields.
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